This list contains the publications of all the members of the BioComputing Unit.
(Actually, the list covers only the publications written as a member of the Unit; for the complete lists, please follow the links within the members homepages.)
To indicate the membership of a certain group, the names within the author list are presented in diferent colors
The groups and their corresponding colors are shown below
Zdobnov,E.M., von-Mering,C., Letunic,I. & Bork,P. (2005).
Consistency of genome-based methods in measuring Metazoan evolution. FEBS Letters, 579, 3355-3361
Suyama,M., Torrents,D. & Bork,P. (2004).
BLAST2GENE: a comprehensive conversion of BLAST output into independent genes and gene fragments. . Bioinformatics, 20, 1968-1970
Perez,A.J., Thode,G., Bork,P. & Andrade,M. (2004).
Gene annotation from scientific literature using mappings between keywords. Bioinformatics, 20, 2084-2091
Krause,R., von-Mering,C., Bork,P. & Dandekar,T. (2004).
Shared components in protein complexes: common phenomena or biochemical artifacts?. Bioessays, 18, 1333-1343
Korbel,J., von-Mering,C., Jensen,L.J. & Bork,P. (2004).
Conservation of bidirectionally transcribed genes in prokaryotes predicts gene regulation. Biotech., 22, 911-917
Koehl,A., Schmidt,N., Rieger,A., Pilgram,S.M., Letunic,I., Bork,P., Soto,F., Friauf,E. & Nothwang,H.G. (2004).
Gene expression profiling of the rat superior olivary complex using serial analysis of gene expression . Eur. J. Nerosci., 20, 3244-3258
Jensen,L.J., Lagarde,J., von-Mering,C. & Bork,P. (2004).
ArrayProspector: A Web resource of functional associations inferred from microarray expression data . Nucleic Acids Res., 32, W445-W448
Bork,P. (2004).
Quality analysis and integration of large scale molecular data sets. Drug Discovery Today (TARGETS) , 3, 51-56
Hermjakob,H. (2004).
The HUPO PSI Molecular Interaction Format: a community standard for the representation of protein interaction data . Nature Biotech., 22, 177-183
Harrington,E.D., Boue,S., Valcarcel,J., Reich,J.G. & Bork,P. (2004).
Estimating rates of alternative splicing in mammals and invertebrates. Nature Genetics, 36, 916-917
Gibbs-RA,e.t. (2004).
The genome sequence of the brown Norwegian Rat yields insight into mammalian evolution . Nature, 428, 493-521
(Rat genome sequencing project consortium; 220 authors)
Forler,D., Rabut,G., Ciccarelli,F.D., Kecher,T., Rode,M., Bork,P., Wilm,M., Ellenberg,J. & Izaurralde,E. (2004).
RanBP2/Nup358 provides a major binding site for NXF1:p15 dimers at the nuclear pore complex and functions in nuclear mRNA export. Mol. Cell. Biol., 24, 1155-1167
Doerks,T., von-Mering,C. & Bork,P. (2004).
Function prediction for hypotical bacterial proteins using genomic context. Nucleic Acid Res., 32, 6321-6326
Doerks,T., von-Mering,C., Andrade,M.A. & Lathe,W. (2004).
Predicting the target processes of transcription regulators. Trends Genetics, 30, 126-131
Crass,T. & et,a.l. (2004).
The Helmholtz network for Bioinformatics: an integrative web portal for bioinformatics resources. Bioinformatics, 20, 268-270
48 authors!
Bork,P., Jensen,L.J., von-Mering,C., Ramani,A.K., Lee,I. & Marcotte,E.M. (2004).
Protein interaction networks from yeast to man. Curr.Opin.Struct.Biol., 14, 292-299
Bork,P. & Orengo,C. (2004).
Sequences and structures in context (editorial). Curr.Opin.Struct.Biol., 14, 261-263
Aloy,P., Boettcher,B., Leutwein,C., Mellwig,C., Fischer,S., Gavin,A.C., Bork,P. & Serrano,L. (2004).
Structure-based assembly of protein complexes in yeast. Science, 303, 2026-2029
Wattarujeekrit,T., Shah,P. & Collier,N. (2004).
PASBio: predicate-argument structures for event extraction in molecular biology.. BMC Bioinformatics, 5, 2004-2
BACKGROUND: The exploitation of information extraction (IE), a technology aiming to provide instances of structured representations from free-form text, has been rapidly growing within the molecular biology (MB) research community to keep track of the latest results reported in literature. IE systems have traditionally used shallow syntactic patterns for matching facts in sentences but such approaches appear inadequate to achieve high accuracy in MB event extraction due to complex sentence structure. A consensus in the IE community is emerging on the necessity for exploiting deeper knowledge structures such as through the relations between a verb and its arguments shown by predicate-argument structure (PAS). PAS is of interest as structures typically correspond to events of interest and their participating entities. For this to be realized within IE a key knowledge component is the definition of PAS frames. PAS frames for non-technical domains such as newswire are already being constructed in several projects such as PropBank, VerbNet, and FrameNet. Knowledge from PAS should enable more accurate applications in several areas where sentence understanding is required like machine translation and text summarization. In this article, we explore the need to adapt PAS for the MB domain and specify PAS frames to support IE, as well as outlining the major issues that require consideration in their construction. RESULTS: We introduce PASBio by extending a model based on PropBank to the MB domain. The hypothesis we explore is that PAS holds the key for understanding relationships describing the roles of genes and gene products in mediating their biological functions. We chose predicates describing gene expression, molecular interactions and signal transduction events with the aim of covering a number of research areas in MB. Analysis was performed on sentences containing a set of verbal predicates from MEDLINE and full text journals. Results confirm the necessity to analyze PAS specifically for MB domain. CONCLUSIONS: At present PASBio contains the analyzed PAS of over 30 verbs, publicly available on the Internet for use in advanced applications. In the future we aim to expand the knowledge base to cover more verbs and the nominal form of each predicate.
Korbel,J.O., Jensen,L.J., von-Mering,C. & Bork,P. (2004).
Analysis of genomic context: prediction of functional associations from conserved bidirectionally transcribed gene pairs. Nat. Biotechnol., 22, 911-917
Pena,R.N., Webster,J., Kwan,S., Korbel,J.O. & Whitelaw,B.A. (2004).
Transgene methylation in mice reflects copy number but not expression level. Mol. Biotechnol., 26, 215-220
Astola,N., Ciccarelli,F.D., Shah,P.K., Bork,P. & Andrade,M.A. (2003).
A protocol for the update of references to scientific literature in biological databases. Appl Bioinformatics, 2, 189-91
Entries in biological databases are usually linked to scientific references. To generate those links and to keep them up-to-date, database maintainers have to continuously scan the scientific literature to select references that are relevant for each single database entry. The continuous growth of both the corpus of scientific literature and the size of biological databases makes this task very hard. We present a protocol intended to assist the updating of an existing set of literature (abstract) links from a single database entry with new references. It consists of taking the set of MEDLINE neighbour references of the existing linked abstracts and evaluating their relevance according to the existing set of abstracts. To test the applicability of the algorithm, we did a simple benchmark of the system using the references associated with the entries of a protein domain database. Human experts found the references that the algorithm scored highly were more relevant to the database entry than those scored lowly, suggesting that the algorithm was useful.
Andrade,M.A. (2003).
Bioinformatics and Genomes: Current Perspectives.. 1-227
Horizon Scientific Press, UK
Apweiler,R., Attwood,T.K., Bairoch,A., Barrell,D., Bateman,A., Binns,D., Biswas,M., Bradley,P., Bork,P., Bucher,P., Copley,R.R., Courcelle,E., Das,U., Durbin,R., Falquet,L., Fleischmann,W., Haft,D., Harte,N., Hulo,N., Kahn,D., Kanapin,A., Krestyaninova,M., Lopez,R., Letunic,I., Lonsdale,D., Silventoinen,V., Orchard,S.E., Pagni,M., Peyruc,D., Ponting,C.P., Selengut,J.D., Servant,F., Sigrist,C.J., Vaughan,R. & Zdobnov,E.M. (2003).
The InterPro Database, 2003 brings increased coverage and new features. Nucleic Acid Research, 31, 315-318
Boue,S., Letunic,I. & Bork,P. (2003).
Alternative splicing and evolution.. Bioessays, 25, 1031-1034
Ciccarelli,F.D., Bork,P. & Kerkhoff,E. (2003).
The KIND module: a putative signalling domain evolved from the C lobe of the protein kinase fold. Trends Biochem. Sci., 28, 349-352
Ciccarelli,F.D., Proukakis,C., Patel,H., Cross,H., Azam,S., Patton,M.A., Bork,P. & Crosby,A.H. (2003).
The identification of a conserved domain in both spartin and spastin, genes mutated in hereditary spastic paraplegia.. Genomics, 81, 437-441
Gatfield,D., Unterholzner,L., Ciccarelli,F.D., Bork,P. & Izaurralde,E. (2003).
Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways. Embo J., 22, 3960-3970
Hillier,L.W., Fulton,R.S., Fulton,L.A., Graves,T.A., Pepin,K.H., Layman,D., Maas,J., Jaeger,S., Walker,R., Wylie,K., Sekhon,M., Becker,M.C., Schaller,M.E., Fewell,G.A., Delehaunty,K.D., Miner,T.L., Nash,W.E., Cordes,M., Du,H., Sun,H., Edwards,J., Ali,J., Andrews,S., Isak,A., Vanbrunt,A., Nguyen,C., Du,F., Lamar,B., Courtney,L., Kalicki,J., Ozersky,P., Bielicki,L., Scott,K., Holmes,A., Harkins,R., Harris,A., Strong,C.M., Hou,S., Tomlinson,C., Leonard,S., Rohlfing,T., Rock,S.M., Abbott,A., Minx,P., Maupin,R., Strowmatt,C., Latreille,P., Miller,N., Johnson,D., Murray,J., Woessner,J.P., Wendl,M.C., Yang,S.P., Schultz,B.R., Wallis,J.W., Spieth,J., Bieri,T.A., Nelson,J.O., Berkowicz,N., Wohldmann,P.E., Cook,L.L., Hickenbotham,M.T., Eldred,J., Williams,D., Bedell,J.A., Mardis,E.R., Clifton,S.W., Chissoe,S.L., Marra,M.A., Raymond,C., Haugen,E., Gillett,W., Zhou,Y., James,R., Phelps,K., Iadanoto,S., Bubb,K., Simms,E., Levy,R., Clendenning,J., Kaul,R., Kent,W.J., Furey,T.S., Baertsch,R.A., Brent,M.R., Keibler,E., Flicek,P., Bork,P., Suyama,M., Bailey,J.A., Portnoy,M.E., Torrents,D., Chinwalla,A.T., Gish,W.R., Eddy,S.R., McPherson,J.D., Olson,M.V., Eichler,E.E., Green,E.D., Waterston,R.H. & Wilson,R.K. (2003).
The DNA sequence of human chromosome 7.. Nature, 424, 157-164
Huynen,M.A., Snel,B., von-Mering,C. & Bork,P. (2003).
Function prediction and protein networks. Curr. Opin. Cell Biol., 15, 191-198
Iliopoulos,I., Tsoka,S., Andrade,M.A., Enright,A.J., Poullet,P., Promponas,V., Liakopoulos,T., Palaios,G., Hamodrakas,S., Tamames,J., Yagnik,A.T., Tramontano,A., Blaschke,C., Valencia,A., Brett,D., Martin,D., Leroy,C., Sander,C. & Ouzounis,C.A. (2003).
Evaluation of annotation strategies using an entire genome sequence. Bioinformatics, 19, 717-726
Kanehisha,M. & Bork,P. (2003).
Bioinformatics in the postgenomic era. Nature Genetics, 33, 305-310
Kriventseva,E.V., Koch,I., Apweiler,R., Vingron,M., Bork,P., Gelfand,M.S. & Sunyaev,S. (2003).
Increase of functional diversity by alternative splicing. Trends Genet., 2003, 124-128
Krause,R., von-Mering,C. & Bork,P. (2003).
A comprehensive set of protein complexes in yeast: mining large scale protein-protein interaction screens. Bioinformatics, 19, 1901-1908
Linding,R., Jensen,L.J., Diella,F., Bork,P., Gibson,T.J. & Russell,R.B. (2003).
Protein disorder prediction: implications for structural proteomics. Structure, 11, 11453-1459
Morett,E., Korbel,J.O., Rajan,E., Olvera,L., Olvera,M., Schmidt,S., Snel,B. & Bork,P. (2003).
Systematic discovery of analogous enzymes in thiamin biosynthesis. Nat Biotechnol, 21, 790-795
Morett,E., Saab-Rincon,G., Merino,E., Bork,P., Rajan,E., Olvera,L. & Olvera,M. (2003).
High rate of gene displacement in vitamine biosynthetic pathways. In: Bioinformatics and genomes. 69-79
(M. Andrade) Horizon Sci. Press
Mulder,N.J., Apweiler,R., Attwood,T.K., Bairoch,A., Barrell,D., Bateman,A., Binns,D., Biswas,M., Bradley,P., Bork,P., Bucher,P., Copley,R.R., Courcelle,E., Das,U., Durbin,R., Falquet,L., Fleischmann,W., Griffiths-Jones,S., Haft,D., Harte,N., Hulo,N., Kahn,D., Kanapin,A., Krestyaninova,M., Lopez,R., Letunic,I., Lonsdale,D., Silventoinen,V., Orchard,S.E., Pagni,M., Peyruc,D., Ponting,C.P., Selengut,J.D., Servant,F., Sigrist,C.J., Vaughan,R. & Zdobnov,E.M. (2003).
The InterPro Database, 2003 brings increased coverage and new features.. Nucleic Acids Res, 31, 315-318
http://www.ebi.ac.uk/interpro ftp://ftp.ebi.ac.uk/pub/databases/interpro
Netzel,R., Bork,P. & Andrade,M.A. (2003).
The way we write. EMBO Rep., 4, 446-451
Perez-Iratxeta,C., Perez,A.J., Bork,P. & Andrade,M.A. (2003).
Update on XplorMed: a web server for exploring scientific literature.. Nucleic Acids Res., 31, 3866-3868
http://www.bork.embl-heidelberg.de/xplormed/
Puntervoll,P., Linding,R., Gemund,C., Mattingsdal,M., Cameron,S., Martin,D.M., Ausiello,G., Brannetti,B., Costantini,A., Ferre,F., Maselli,V., Via,A., Cesareni,G., Diella,F., Wyrwicz,L., Ramu,C., McGuigan,C., Gudavalli,R., Letunic,I., Bork,P., Rychlewski,L., Kuster,B., Hunter,W.N., Aasland,R. & Gibson,T.J. (2003).
ELM server: A new resource for investigating short functional sites in modular eukaryotic proteins. Nucleic Acids Res., 31, 3625-3630
Schmidt,S., Sunyaev,S., Bork,P. & Dandekar,T. (2003).
Metabolites: a helping hand for pathway evolution?. Trends Biochem Sci., 28, 336-341
Shah,P.K., Perez-Iratxeta,C., Bork,P. & Andrade,M.A. (2003).
Information extraction from full text scientific articles: Where are the keywords?. BMC Bioinformatics, 4, 20-20
Shevchenko,A., Sunyaev,S., Liska,A., Bork,P. & Shevchenko,A. (2003).
Nanoelectrospray tandem mass spectrometry and sequence similarity searching for identification of proteins from organisms with unknown genomes.. Methods Mol Biol., 211, 221-234
Snel,B., Mering,C. & Bork,P. (2003).
Function prediction and protein networks. Current Opinion Cell Biology, 15, 191-198
Sunyaev,S., Kondrashov,F.A., Bork,P. & Ramensky,V. (2003).
Impact of selection, mutation rate and genetic drift on human genetic variation. Hum Mol Genet., 12, 3325-3330
Torrents,D., Suyama,M., Zdobnov,E. & Bork,P. (2003).
A genome-wide survey of human pseudogenes. Genome Res. , 13, 2559-2567
Torrents,D., Suyama,M. & Bork,P. (2003).
Pseudogenes and Genomes. In: Bioinformatics and genomes. 197-209
(M. Andrade) Horizon Sci. Press
Von-Mering,C., Zdobnov,E.M., Tsoka,S., Ciccarelli,F.D., Ouzounis,C.A. & Bork,P. (2003).
Genome evolution reveals biochemical networks and functional modules. Proc. Natl. Acad. Sci USA , 26, 15428-15433
Woerner,S.M., Benner,A., Sutter,C., Schiller,M., Yuan,Y.P., Keller,G., Bork,P., Doeberitz,M.K. & Gebert,J.F. (2003).
Pathogenesis of DNA repair-deficient cancers: a statistical meta-analysis of putative Real Common Target genes.. Oncogene, 22, 2226-2235
von-Mering,C., Huynen,M., Jaeggi,D., Schmidt,S., Bork,P. & Snel,B. (2003).
STRING: a database of predicted functional associations between proteins.. Nucleic Acids Res, 31, 258-261
http://www.bork.embl-heidelberg.de/STRING/
Aloy,P., Ciccarelli,F.D., Leutwein,C., Gavin,A.C., Bork,P., Bottcher,B. & Russell,R.B. (2002).
A complex prediction: three-dimensional model of the yeast exosome.. EMBO Rep., 3, 628-635
Andrade,M.A., Ciccarelli,F.D., Perez-Iratxeta,C. & Bork,P. (2002).
NEAT: A domain duplicated in
genes near the components of a putative Fe3+ siderophore transporter from Gram-positive pathogenic bacteria. Genome Biology, 3, 47-1
Bordo,D. & Bork,P. (2002).
The rhodanese/Cdc25 phosphatase superfamily. Sequence-structure-function relations.. EMBO Rep., 3, 741-746
Bork,P. (2002).
Comparative analysis of protein interaction networks.. Bioinformatics, 18, 64-64
Brett,D., Pospisil,H., Valcarcel,J., Reich,J. & Bork,P. (2002).
Alternative splicing and genome complexity. Nat Genet, 30, 29-30
Christophides,G.K., Zdobnov,E., Barillas-Mury,C., Birney,E., Blandin,S., Blass,C., Brey,P.T., Collins,F.H., Danielli,A., Dimopoulos,G., Hetru,C., Hoa,N.T., Hoffmann,J.A., Kanzok,S.M., Letunic,I., Levashina,E.A., Loukeris,T.G., Lycett,G., Meister,S., Michel,K., Moita,L.F., Muller,H.M., Osta,M.A., Paskewitz,S.M., Reichhart,J.M., Rzhetsky,A., Troxler,L., Vernick,K.D., Vlachou,D., Volz,J., von-Mering,C., Xu,J., Zheng,L., Bork,P. & Kafatos,F.C. (2002).
Immunity-related genes and gene families in Anopheles gambiae.. Science, 298, 159-165
Ciccarelli,F., Copley,R.R., Doerks,T., Russell,R.B. & Bork,P. (2002).
CASH--a beta-helix domain widespread among carbohydrate-binding proteins. Trends Biochem Sci, 27, 59-62
Ciccarelli,F., Doerks,T. & Bork,P. (2002).
AMOP, a protein module alternatively spliced in cancer cells. Trends Biochem Sci , 27, 113-115
Copley,R.R., Doerks,T., Letunic,I. & Bork,P. (2002).
Protein domain analysis in the era of complete genomes. FEBS Lett, 513, 129-134
Copley,R.R., Letunic,I. & Bork,P. (2002).
Genome and protein evolution in eukaryotes. Curr Opin Chem Biol, 6, 39-45
Copley,R.R., Ponting,C.P., Schultz,J. & Bork,P. (2002).
Sequence analysis of multidomain proteins: past perspectives and future directions.. Adv Protein Chem, 61, 75-98
Dandekar,T., Snel,B., Schmidt,S., Lathe,W., Suyama,M., Huynen,M. & Bork,P. (2002).
Comparative Genome Analysis of the Mollicutes. In: Molecular Biology and Pathogenicity of Mycoplasmas. 255-278
(Razin and Herrmann) Kluwer Academic/Plenum Publishers, New York
Doerks,T., Copley,R.R., Schultz,J., Ponting,C.P., & Bork,P. (2002).
Systematic identification of novel protein domain families associated with nuclear functions. Genome Res, 12, 47-56
Doerks,T., Huber,S., Buchner,E. & Bork,P. (2002).
BSD: a novel domain in transcription factors and synapse-associated proteins. Trends Biochem Sci, 27, 168-170
Fredman,D., Siegfried,M., Yuan,Y.P., Bork,P., Lehvaslaiho,H., & Brookes,A.J. (2002).
HGVbase: a human sequence variation database emphasizing data quality and a broad spectrum of data sources.. Nucleic Acids Res, 30, 387-391
Gavin,A.C., Bosche,M., Krause,R., Grandi,P., Marzioch,M., Bauer,A., Schultz,J., Rick,J.M., Michon,A.M., Cruciat,C.M., Remor,M., Hofert,C., Schelder,M., Brajenovic,M., Ruffner,H., Merino,A., Klein,K., Hudak,M., Dickson,D., Rudi,T., Gnau,V., Bauch,A., Bastuck,S., Huhse,B., Leutwein,C., Heurtier,M.A., Copley,R.R., Edelmann,A., Querfurth,E., Rybin,V., Drewes,G., Raida,M., Bouwmeester,T., Bork,P., Seraphin,B., Kuster,B., Neubauer,G. & Superti-Furga,G. (2002).
Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature, 415, 141-147
Giraldez,A.J., Copley,R.R. & Cohen,S.M. (2002).
HSPG modification by the secreted enzyme Notum shapes the Wingless morphogen gradient. Dev Cell, 2, 667-676
Holt,R.A., Subramanian,G.M., Halpern,A., Sutton,G.G., Charlab,R., Nusskern,D.R., Wincker,P., Clark,A.G., Ribeiro,J.M., Wides,R., Salzberg,S.L., Loftus,B., Yandell,M., Majoros,W.H., Rusch,D.B., Lai,Z., Kraft,C.L., Abril,J.F., Anthouard,V., Arensburger,P., Atkinson,P.W., Baden,H., de-Berardinis,V., Baldwin,D., Benes,V., Biedler,J., Blass,C., , Bolanos,R., Boscus,D., Barnstead,M., Cai,S., Center,A., Chatuverdi,K., Christophides,G.K., Chrystal,M.A., Clamp,M., Cravchik,A., Curwen,V., Dana,A., Delcher,A., Dew,I., Evans,C.A., Flanigan,M., Friedli,L., Gu,Z., Guan,P., Guigo,R., Hillenmeyer,M.E., Hladun,S.L., Hogan,J.R., Hong,Y.S., Hoover,J., Jaillon,O., Ke,Z., Kodira,C., Kokoza,E., Koutsos,A., Letunic,I., Levitsky,A., Liang,Y., Lin,J.J., Lobo,N.F., Lopez,J.R., Malek,J.A., McIntosh,T.C., Meister,S., Miller,J., Mobarry,C., Mongin,E., Murphy,S.D., Pfannkoch,C., Qi,R., Regier,M.A., Remington,K., Shao,H., Sharakhova,M.V., Sitter,C.D., Shetty,J., Smith,T.J., Strong,R., Sun,J., Thomasova,D., Ton,L.Q., Topalis,P., Tu,Z., Unger,M.F., Walenz,B., Wang,A., Wang,J., Wang,M., Wang,X., Woodford,K.J., Wortman,J.R., Wu,M., Yao,A., Zdobnov,E.M., Zhang,H., Zhao,Q., Zhao,S., Zhu,S.C., Zhimulev,I., Coluzzi,M., della-Torre,A., Roth,C.W., Louis,C., Kalush,F., Mural,R.J., Myers,E.W., Adams,M.D., Smith,H.O., Broder,S., Gardner,M.J., Fraser,C.M., Birney,E., Bork,P., Brey,P.T., Venter,J.C., Weissenbach,J., Kafatos,F.C., Collins,F.H. & Hoffman,S.L. (2002).
The genome sequence of the malaria mosquito Anopheles gambiae.. Science, 298, 129-149
Kloor,M., Bork,P., Duwe,A., Klaes,R., von-Knebel-Doeberitz,M. & Ridder,R. (2002).
Identification and characterization of UEV3, a human cDNA with similarities to inactive E2 ubiquitin-conjugating enzymes.. Biochim Biophys Acta, 1579, 219-224
Korbel,J.O. (2002).
On the regulation of transcription in eukaryotes and methods for finding DNA regulatory elements using bioinformatics. In: Sitzungsberichte der Gesellschaft Naturforschender Freunde zu Berlin. 41, 57-66
(Walter Sudhaus) Goecke & Evers, Keltern
Korbel,J.O., Snel,B., Huynen,M.A. & Bork,P. (2002).
SHOT: a web server for the construction of genome phylogenies. Trends Genet, 18, 158-162
http://www.bork.embl-heidelberg.de/SHOT
Letunic,I., Copley,R.R. & Bork,P. (2002).
Common exon duplication in animals and its role in alternative splicing. Hum Mol Genet, 11, 1561-1567
Letunic,I., Goodstadt,L., Dickens,N.J., Doerks,T., Schultz,J., Mott,R., Ciccarelli,F., Copley,R.R., Ponting,C.P. & Bork,P. (2002).
Recent improvements to the SMART domain-based sequence annotation resource.. Nucleic Acids Res, 30, 242-244
Mott,R., Schultz,J., Bork,P. & Ponting,C.P. (2002).
Predicting protein cellular localization using a domain projection method.. Genome Res., 12, 1168-1174
Mulder,N.J., Apweiler,R., Attwood,T.K., Bairoch,A., Bateman,A., Binns,D., Biswas,M., Bradley,P., Bork,P., Bucher,P., Copley,R., Courcelle,E., Durbin,R., Falquet,L., Fleischmann,W., Gouzy,J., Haft,D., Hermjakob,H., Hulo,N., Kahn,D., Kanapin,A., Krestyaninova,M., Lopez,R., Letunic,I., Orchard,S., Pagni,M., Peyruc,D., Ponting,C.P., Servant,F. & Sigrist,C.J. (2002).
InterPro: an integrated documentation resource for protein families, domains and functional sites.. Brief Bioinform, 3, 225-235
Muro,E.M., Andrade,M.A. & Morán,F. (2002).
A self-organizing model for the development of orientation selectivity and ocular dominance patterns in the visual nervous system. Neural Network World, 12, 319-332
Patel,H., Cross,H., Proukakis,C., Hershberger,R., Bork,P., Ciccarelli,F.D., Patton,M.A., McKusick,V.A. & Crosby,A.H. (2002).
SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia.. Nat Genet, 31, 347-348
Perez-Iratxeta,C. & Andrade,M.A. (2002).
Worldwide scientific publishing activity. Science, 297, 2002-23
Perez-Iratxeta,C., Bork,P. & Andrade,M.A. (2002).
Exploring MEDLINE abstracts with XplorMed.. Drugs of Today, 38, 381-389
Perez-Iratxeta,C., Bork,P. & Andrade,M.A. (2002).
Association of genes to genetically inherited diseases using data mining. Nature Genetics, 31, 316-319
G2D server
Perez-Iratxeta,C., Keer,H.S., Bork,P. & Andrade,M.A. (2002).
Computing fuzzy associations for the analysis of biological literature. BioTechniques, 32, 1380-1385
Ramensky,V., Bork,P. & Sunyaev,S. (2002).
Human non-synonymous SNPs: server and survey.. Nucleic Acids Res., 30, 3894-900
Schell,M.A., Karmirantzou,M., Snel,B., Vilanova,D., Berger,B., Pessi,G., Zwahlen,M.C., Desiere,F., Bork,P., Delley,M., Pridmore,R.D. & Arigoni,F. (2002).
The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract.. Proc Natl Acad Sci U S A, 99, 14422-14427
Schmidt,S., Bork,P. & Dandekar,T. (2002).
A versatile structural domain analysis server using profile weight matrices.. J Chem Inf Comput Sci., 42, 405-407
AnDom-Server
Snel,B., Bork,P. & Huynen,M. (2002).
Conservation of gene co-regulation in prokaryotes and eukaryotes.
. Trends Biotechnol, 20, 410-410
Snel,B., Bork,P. & Huynen,M.A. (2002).
The identification of functional modules from the genomic association of genes. Proc Natl Acad Sci USA, 99, 5890-5895
Snel,B., Bork,P., & Huynen,M.A. (2002).
Genomes in flux: the evolution of archaeal and proteobacterial gene content. Genome Res, 12, 17-25
Thomasova,D., Ton,L.Q., Copley,R.R., Zdobnov,E.M., Wang,X., Hong,Y.S., Sim,C., Bork,P., Kafatos,F.C. & Collins,F.H. (2002).
Comparative genomic analysis in the region of a major Plasmodium-refractoriness locus of Anophelesgambiae. Proc Natl Acad Sci USA, 99, 8179-8184
Waterston,R.H., Lindblad-Toh,K., Birney,E., Rogers,J., Abril,J.F., Agarwal,P., Agarwala,R., Ainscough,R., Alexandersson,M., An,P., Antonarakis,S.E., Attwood,J., Baertsch,R., Bailey,J., Barlow,K., Beck,S., Berry,E., Birren,B., Bloom,T., Bork,P., Botcherby,M., Bray,N., Brent,M.R., Brown,D.G., Brown,S.D., Bult,C., Burton,J., Butler,J., Campbell,R.D., Carninci,P., Cawley,S., Chiaromonte,F., Chinwalla,A.T., Church,D.M., Clamp,M., Clee,C., Collins,F.S., Cook,L.L., Copley,R.R., Coulson,A., Couronne,O., Cuff,J., Curwen,V., Cutts,T., Daly,M., David,R., Davies,J., Delehaunty,K.D., Deri,J., , Dermitzakis,E.T., Dewey,C., Dickens,N.J., Diekhans,M., Dodge,S., Dubchak,I., Dunn,D.M., Eddy,S.R., Elnitski,L., Emes,R.D., Eswara,P., Eyras,E., Felsenfeld,A., Fewell,G.A., Flicek,P., Foley,K., Frankel,W.N., Fulton,L.A., Fulton,R.S., Furey,T.S., Gage,D., Gibbs,R.A., Glusman,G., Gnerre,S., Goldman,N., Goodstadt,L., Grafham,D., Graves,T.A., Green,E.D., Gregory,S., Guigo,R., Guyer,M., Hardison,R.C., Haussler,D., Hayashizaki,Y., Hillier,L.W., Hinrichs,A., Hlavina,W., Holzer,T., Hsu,F., Hua,A., Hubbard,T., Hunt,A., Jackson,I., Jaffe,D.B., Johnson,L.S., Jones,M., Jones,T.A., Joy,A., Kamal,M., , Karlsson,E.K., Karolchik,D., Kasprzyk,A., Kawai,J., Keibler,E., Kells,C., Kent,W.J., Kirby,A., Kolbe,D.L., Korf,I., Kucherlapati,R.S., Kulbokas,E.J., Kulp,D., Landers,T., Leger,J.P., Leonard,S., Letunic,I., Levine,R., Li,J., Li,M., Lloyd,C., Lucas,S., Ma,B., Maglott,D.R., Mardis,E.R., Matthews,L., Mauceli,E., Mayer,J.H., McCarthy,M., McCombie,W.R., McLaren,S., McLay,K., McPherson,J.D., Meldrim,J., Meredith,B., Mesirov,J.P., Miller,W., Miner,T.L., Mongin,E., , Montgomery,K.T., Morgan,M., Mott,R., Mullikin,J.C., Muzny,D.M., Nash,W.E., Nelson,J.O., Nhan,M.N., Nicol,R., Ning,Z., Nusbaum,C., OConnor,M.J., Okazaki,Y., Oliver,K., Overton-Larty,E., Pachter,L., Parra,G., Pepin,K.H., Peterson,J., Pevzner,P., Plumb,R., Pohl,C.S., Poliakov,A., Ponce,T.C., Ponting,C.P., Potter,S., Quail,M., Reymond,A., Roe,B.A., Roskin,K.M., Rubin,E.M., Rust,A.G., Santos,R., Sapojnikov,V., Schultz,B., Schultz,J., Schwartz,M.S., Schwartz,S., Scott,C., Seaman,S., Searle,S., Sharpe,T., Sheridan,A., Shownkeen,R., Sims,S., Singer,J.B., Slater,G., Smit,A., Smith,D.R., Spencer,B., Stabenau,A., Stange-Thomann,N., Sugnet,C., Suyama,M., Tesler,G., Thompson,J., Torrents,D., Trevaskis,E., Tromp,J., Ucla,C., Ureta-Vidal,A., Vinson,J.P., Von-Niederhausern,A.C., Wade,C.M., Wall,M., Weber,R.J., Weiss,R.B., Wendl,M.C., West,A.P., Wetterstrand,K., Wheeler,R., Whelan,S., Wierzbowski,J., Willey,D., Williams,S., Wilson,R.K., Winter,E., Worley,K.C., Wyman,D., Yang,S., Yang,S.P., Zdobnov,E.M., Zody,M.C. & Lander,E.S. (2002).
Initial sequencing and comparative analysis of the mouse genome.. Nature, 420, 520-562
Mouse Genome Sequencing Consortium.
Zdobnov,E.M., von-Mering,C., Letunic,I., Torrents,D., Suyama,M., Copley,R.R., Christophides,G.K., Thomasova,D., Holt,R.A., Subramanian,G.M., Mueller,H.M., Dimopoulos,G., Law,J.H., Wells,M.A., Birney,E., Charlab,R., Halpern,A.L., Kokoza,E., Kraft,C.L., Lai,Z., Lewis,S., Louis,C., Barillas-Mury,C., Nusskern,D., Rubin,G.M., Salzberg,S.L., Sutton,G.G., Topalis,P., Wides,R., Wincker,P., Yandell,M., Collins,F.H., Ribeiro,J., Gelbart,W.M., Kafatos,F.C. & Bork,P. (2002).
Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster.. Science, 298, 149-159
von-Mering,C. & Bork,P. (2002).
Proteinkomplexe und Netzwerke: Neue Herausforderungen für die Proteomik. Genomexpress, 2, 2-4
von-Mering,C. & Bork,P. (2002).
Genome organization: Teamed up for transcription. Nature, 417, 797-798
von-Mering,C., Krause,R., Snel,B., Cornell,M., Oliver,S.G., Fields,S. & Bork,P. (2002).
Comparative assessment of large-scale data sets of protein-protein interactions. Nature, 417, 399-403
Andrade,M.A., Gonzalez-Guzman,M., Serrano,R. & Rodriguez,P.L. (2001).
A combination of the F-box motif and kelch repeats defines a large Arabidopsis family of F-box proteins. Plant Mol Biol, 46, 603-614
Andrade,M.A., Muro,E.M. & Moran,F. (2001).
Simulation of plasticity in the adult visual cortex.. Biological Cybernetics, 84, 445-451
Andrade,M.A., Perez-Iratxeta,C. & Ponting,C.P. (2001).
Protein repeats: structures, functions and evolution.. Journal of Structural Biology, 84, 445-451
Andrade,M.A., Petosa,C., ODonoghue,S.I., Müller,C.W. & Bork,P. (2001).
Comparison of ARM and HEAT repeat proteins. J. Mol. Biol., 309, 1-18
[REP server]
Becker,S., Gehrsitz,A., Bork,P., Buchner,S. & Buchner,E. (2001).
The black-pearl gene of Drosophila defines a novel conserved protein family and is required for larval growth and survival.. Gene, 262, 15-22
Bork,P. & Copley,R. (2001).
The draft sequences. Filling in the gaps.. Nature, 409, 818-820
news and views
Bork,P. & Copley,R. (2001).
Genome speak. Nature, 409, 815-815
..just a glossary
Dandekar,T. (2001).
Trends in Biochemical Systems (Review). Trends in Biochemical Sciences, 26, 637-637
Dandekar,T., Du,F., Schirmer,R.H. & Schmidt,S. (2001).
Medical target prediction from genome sequence: combining different sequence analysis algorithms with expert knowledge and input from artificial intelligence approaches.. Comput Chem, 26, 15-21
Doerks,T., Copley,R. & Bork,P. (2001).
DDT - a novel domain in different transcription and chromosome remodeling factors.. Trends Biochem Sci., 26, 145-146
Huynen,M., Snel,B. & Bork,P. (2001).
Inversions and the evolution of eukaryotic gene order. Treneds Genetics, 17, 304-306
Huynen,M., Snel,B., Bork,P. & Gibson,T.J. (2001).
The phylogenetic distribution of frataxin indicates a role in iron-sulfur cluster protein ssembly . Hum.Mol.Genet., 10, 2463-2468
Iliopoulos,I., Tsoka,S., Andrade,M.A., Janssen,P., Audit,B., Tramontano,A., Valencia,A., Leroy,C., Sander,C. & Ouzounis,C.A. (2001).
Genome sequences and great expectations. Genome Biology, 2, 001-1
[e-version@Genome Biology]
Iyer,L.M., Aravind,L., Bork,P., Hofmann,K., Mushegian,A.R., Zhulin,I.B. & Koonin,E.V. (2001).
Quod erat demonstrandum? They mystery of experimental validation of apparently erroneous computational analyses of protein sequences. . Genome Biology, 2, 1-11
Kerkhoff,E., Simpson,J.C., Leberfinger,C.B., Otto,I.M., Doerks,T., Bork,P., Rapp,U.R., Raabe,T. & Pepperkok,R. (2001).
The Spir actin organizers are involved in vesicle transport processes. Curr Biol, 11, 1963-1968
Lander,E.S. & Et,A.L. (2001).
Initial sequencing and analysis of the human genome. Nature, 409, 860-921
Richard Copley, Tobias Doerks, Joerg Schultz and Peer Bork from the group are among the 250 listed authors
Lathe,W. & Bork,P. (2001).
Evolution of the tufA: multiple duplications, losses and gene conversions. FEBS Lett., 502, 113-116
Linnebacher,M., Gebert,J., Rudy,W., Woerner,S., Yuan,Y.P., Bork,P. & von-Knebel-Doeberitz,M. (2001).
Frameshift peptide-derived T-cell epitopes: A source of novel tumor-specific antigens.. Int. J. Cancer, 93, 6-11
Perez-Iratxeta,C., Bork,P. & Andrade,M.A. (2001).
XplorMed: a tool for exploring MEDLINE abstract. Trends Biochem Sci, 26, 573-575
Server
Ponting,C.P., Mott,R., Bork,P. & Copley,R.R. (2001).
Novel protein domains and repeats in Drosophila melanogaster: insights into structure, function, and evolution. Genome Res, 11, 1996-2008
Schultz,J., Jones,T., Bork,P., Sheer,D., Blencke,S., Steyrer,S., Wellbrock,U., Bevec,D., Ullrich,A. & Wallasch,C. (2001).
Molecular Characterization of a cDNA Encoding Functional Human CLK4 Kinase and Localization to Chromosome 4q35. Genomics, 71, 368-370
Shevchenko,A., Loboda,A., Sunyaev,S., Shevchenko,A., Bork,P., Ens,W. & Standing,K.G. (2001).
Charting the proteomes of organisms with unsequenced genomes by MALDI-quadrupole time-of flight mass spectrometry and BLAST homology searching. Analyt. Chem., 73, 1917-1926
Sunyaev,S., Lathe,W. & Bork,P. (2001).
Integration of genome data and protein structures: prediction of protein folds, protein interactions and
'molecular phenotypes' of single nucleotide polymorphisms.. Curr Opin Struct Biol., 11, 125-130
Sunyaev,S., Ramensky,V., Koch,I., Lathe,W., Kondrashov,A.S. & Bork,P. (2001).
Prediction of deleterious human alleles.. Hum Mol Genet, 10, 591-567
Suyama,M. & Bork,P. (2001).
Evolution of prokaryotic gene order: genome rearrangements in closely related species. Trends Genet., 17, 10-13
Wang,R., Zheng,L., Toure,Y.T., Dandekar,T. & Kafatos,F.C. (2001).
When genetic distance matters: Measuring genetic differentiation at microsatellite loci in whole genome scans of recent and incipient mosquito species. . Proc. Natl. Acad. Sci. USA, 98, 10769-74
Woerner,S.M., Gebert,J., Yuan,Y.P., Sutter,C., Ritter,R., Bork,P. & von-Knebel-Doeberitz,M. (2001).
Systematic identification of genes with coding microsatellites mutated in DNA mismatch repair-deficient cancer cells.. Int. J. Cancer, 93, 12-19
Andrade,M.A. & Bork,P. (2000).
Automated extraction of information in molecular biology. FEBS Letters, 476, 12-17
[web appendix]
Andrade,M.A., Ponting,C.P., Gibson,T.J. & Bork,P. (2000).
Homology-based method for identification of protein repeats using statistical significance estimates. J. Mol. Biol., 298, 521-537
[REP-server] [Web appendix]
Bork,P. & Eisenberg,D. (2000).
Genome and proteome informatics. Curr.Opin.Struct.Biol., 10, 341-342
Bork,P. (2000).
Powers and pitfalls in sequence analysis: the 70% hurdle.. Genome Res., 10, 398-400
Brett,D., Hanke,J., Lehmann,G., Haase,S., Delbruck,S., Krueger,S., Reich,J. & Bork,P. (2000).
EST comparison indicates 38% of human mRNAs contain possible alternative splice forms. FEBS Lett., 474, 83-86
Brett,D., Lehmann,G., Hanke,J., Gross,S., Reich,J. & Bork,P. (2000).
EST analysis online: WWW tools for detection of SNPs and alternative splice forms. Trends Genet. , 16, 416-418
Brookes,A.J., Lehvaslaiho,H., Siegfried,M., Boehm,J.G., Yuan,Y.P., Sarkar,C.M., Bork,P. & Ortigao,F. (2000).
HGBASE: a database of SNPs and other variations in and around human genes. Nucleic Acids Res., 28, 356-360
Dandekar,T., Huynen,M., Regula,J.T., Zimmermann,C.U., Ueberle,B., Andrade,M.A., Doerks,T., Sanchez-Pulido,L., Snel,B., Suyama,M., Yuan,Y.P., Herrmann,R. & Bork,P. (2000).
Re-annotating the Mycoplasma pneumoniae genome sequence: adding value, function and reading frames. Nucleic Acids Research, 28, 3278-3288
[web appendix.]
Dimopoulos,G., Casavant,T.L., Chang,S., Scheetz,T., Roberts,C., Donohue,M., Schultz,J., Benes,V., Bork,P., Ansorge,W., Soares,M.B. & Kafatos,F.C. (2000).
Anopheles gambiae pilot gene discovery project: Identification of mosquito innate immunity genes from
expressed sequence tags generated from immune-competent cell lines. . Proc Natl Acad Sci U S A, 97, 6619-6624
Doerks,T., Bork,P., Kamberov,E., Makarova,O., Muecke,S. & Margolis,B. (2000).
L27, a novel heterodimerization domain in receptor targeting proteins Lin-2 and Lin-7. Trends Biochem Sci , 25, 317-318
Doerks,T., Strauss,M., Brendel,M. & Bork,P. (2000).
GRAM, a novel domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins.. Trends Biochem Sci, 25, 483-485
Eisenhaber,B., Bork,P., Yuan,Y.P., Loeffler,G. & Eisenhaber,F. (2000).
Automated annotation of GPI anchor sites: case study C. elegans. TIBS, 25, 340-341
The web server: http://www.embl-heidelberg.de/~beisenha/gpi/gpi_server.html .
Herold,A., Suyama,M., Rodrigues,J., Braun,I., Kutay,U., Carmo-Fonseca,M., Bork,P. & Izaurralde,E. (2000).
TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved modular architecture. Mol. Cell. Biol., 20, 9886-9888
Hoersch,S., Leroy,C., Brown,N.P., Andrade,M.A. & Sander,C. (2000).
The GeneQuiz Web server: protein functional analysis through the Web. Trends in Biochemical Sciences, 25, 33-35
Huynen,M.A. & Snel,B. (2000).
Gene and context: Integrative approaches to genome analysis. Advances in Protein Chemistry, 54, 345-379
Huynen,M.A., Snel,B., Lathe,W. & Bork,P. (2000).
Predicting protein function by genomic context: quantitative evaluation and qualitative inferences. Genome Research, 10, 1204-1210
Huynen,M.A., Snel,B., Lathe,W. & Bork,P. (2000).
Exploitation of gene context. Current Opinion in Structural Biology, 10, 366-370
Isaksson,A., Landegren,U., Syvanen,A.C., Bork,P., Stein,C., Ortigao,F. & Brookes,A.J. (2000).
Discovery, scoring and utilization of human single nucleotide polymorphisms: a multidisciplinary problem.. Eur J Hum Genet. , 8, 154-156
Kenealy,M.R., Flouriot,G., Sonntag-Buck,V., Dandekar,T., Brand,H. & Gannon,F. (2000).
The 3'-untranslated region of the human estrogen receptor alpha gene mediates rapid messenger ribonucleic acid turnove. Endocrinology, 141, 2805-2813
Lathe,W.C., Snel,B., & Bork,P. (2000).
Gene context conservation of a higher order than operons. Trends in Biochemical Sciences, 25, 474-9
Operons, co-transcribed and co-regulated contiguous sets of genes, are poorly conserved over short periods of evolutionary time. The gene order, gene content and regulatory mechanisms of operons can be very different, even in closely related species. Here, we present several lines of evidence which suggest that, although an operon and its individual genes and regulatory structures are rearranged when comparing the genomes of different species, this rearrangement is a conservative process. Genomic rearrangements invariably maintain individual genes in very specific functional and regulatory contexts. We call this conserved context an uber-operon.
Otto,I.M., Raabe,T., Rennefahrt,U.E., Bork,P., Rapp,U.R. & Kerkhoff,E. (2000).
The p150-Spir protein provides a link between c-Jun N-terminal kinase function and actin reorganization.. Curr Biol. , 10, 345-348
Ponting,C.P., Schultz,J., Copley,R.R., Andrade,M. & Bork,P. (2000).
Evolution of domain families.. Adv Prot Chem, 54, 185-244
Sanchez-Pulido,L., Yuan,Y.P., Andrade,M.A. & Bork,P. (2000).
NAIL-Network Analysis Interface for Linking HMMER results. Bioinformatics, 16, 656-657
Schultz,J., Copley,R.R., Doerk,T., Ponting,C.P. & Bork,P. (2000).
SMART: a web-based tool for the study of genetically mobile domains. Nucleic Acids Res., 28, 231-234
Schultz,J., Doerks,T., Ponting,C.P., Copley,R.R. & Bork,P. (2000).
More than 1000 putative novel human signalling proteins revealed by EST data mining.. Nat Genet, 25, 201-204
Schuster,S., Fell,D.A. & Dandekar,T. (2000).
A general definition of metabolic pathways useful for
systematic organization and analysis of complex metabolic
networks. Nature Biotechnology, 18, 326-332
N&V on it:A.Cornish-Bowden & M.L.Cardenas (2000) NatureBT 18, 267-268.
Snel,B., Bork,P. & Huynen,M. (2000).
Genome evolution: gene fusion versus gene fission. Trends Genet., 16, 9-11
Snel,B., Lehmann,G., Bork,P. & Huynen,M.A. (2000).
STRING: A web-server to retrieve and display the repeatedly occurring neighbourhood of a gene.. Nucleic Acids Res., 28, 3442-3444
Stutz,F., Bachi,A., Doerks,T., Braun,I.C., Seraphin,B., Wilm,M., Bork,P. & Izaurralde,E. (2000).
REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export. RNA, 6, 638-650
Sunyaev,S., Ramensky,V. & Bork,P. (2000).
Towards a structural basis of human non-synonymous single nucleotide polymorphisms.. Trends Genet., 16, 198-200
Sunyaev,S.R., Hanke,J., Brett,D., Aydin,A., Zastrow,I., Lathe-III,W.C., Bork,P. & Reich,J. (2000).
Individual variation in protein-coding sequences of human genes.. Advances in Protein Chemistry., 54, 409-437
Sunyaev,S.R., Lathe-III,W.C., Ramensky,V.E. & Bork,P. (2000).
SNP frequencies in human genes: an excess of rare alleles and different modes of selection.. Trends in Genetics, 16, 335-337
Suyama,M., Doerks,T., Braun,I.C., Sattler,M., Izaurralde,E. & Bork,P. (2000).
Prediction of structural domains of TAP reveals details of its interaction with p15 and nucleoporins. EMBO Reports, 1, 53-58
Tribble,G., Ahn,Y.T., Lee,J., Dandekar,T. & Jayaram,M. (2000).
DNA recognition, strand selectivity, and cleavage mode during integrase family site-specific
recombination. J Biol Chem, 275, 22255-67
van-Hoek,A., Akhmanova,A.S., Huynen,M.A. & Hackstein,J.H.P. (2000).
A mitochondrial ancestry of the hydrogenosomes of Nyctotherus ovalis.. Mol Biol Evol, 17, 202-206
Adinolfi,S., Bagni,C., Musco,G., Gibson,T., Mazzarella,L. & Pastore,A. (1999).
Dissecting FMR1, the protein responsible for Fragile X syndrome, in its structural and functional domains. RNA, 5, 1248-1258
Altenberg-Greulich,B. & Vriend,G. (1999).
Molecular modelling and macromolecular visualisation of the position of the Phyllochinone Vitamine K1 in Photosystem I by the help of the program WHAT IF. Protein Science, 8, 46-46
This was a poster abstract
Andrade,M.A. (1999).
Position-specific annotation of protein function based on multiple homologs. ISMB, 7, 28-33
Andrade,M.A., Brown,N.P., Leroy,C., Hoersch,S., de-Daruvar,A., Reich,C., Franchini,A., Tamames,J., Valencia,A., Ouzounis,C. & Sander,C. (1999).
Automated genome sequence analysis and annotation. Bioinformatics, 15, 391-412
Andrade,M.A., Ouzounis,C., Sander,C., Tamames,J. & Valencia,A. (1999).
Complete genomes and the ubiquitous presence of functional classes in the three domains of life. J. Mol. Evol., 49, 551-557
[web appendix]
Bansal,A. & Bork,P. (1999).
Applying logic programming to derive novel functional information of genomes. In: Lecture notes in computer sciences: Practical aspects of declarative languages. 1551, 275-289
(Gupta, G.) Springer, New York
Blaschke,C., Andrade,M.A., Ouzounis,C. & Valencia,A. (1999).
Automatic extraction of biological information from Scientific text: protein-protein interactions. ISMB, 7, 60-67
Bork,P. & Huynen,M. (1999).
A point of entry into genomics (book review). Nature Genet., 23, 273-273
Bork,P. (1999).
Bioinformatik (editorial). Biospektrum, 3, 172-172
Bork,P., Dandekar,T., Snel,B. & Huynen,M.A. (1999).
Genome Comparsions to Monitor Molecular Evolution. In: Microbial Evolution and Infection. 80-92
(Goebel, U.B., Ruf, B.R.) Einhorn-Presse Verlag Reinbek
Bork,P., Doerks,T., Springer,T.A. & Snel,B. (1999).
Domains in plexins: links to integrins and transcription factors.. Trends Biochem Sci , 24, 261-263
Boteva,R., Visser,A.J.W.G., Filippi,B., Vriend,G., Veenhuis,M. & van-der-Klei,I.J. (1999).
Conformational transitions accompanying oligomerization of yeast alcohol oxidase, a peroxisomal
flavoenzyme. Biochemistry , 38, 5034-5044
Homology modelling suggested the fluorescence experiments that answered questions
regarding the oligomerization of AO.
Castresana,J. & Moreira,D. (1999).
Respiratory chains in the last common ancestor of living organisms. J. Mol.
Evol., 49, 453-460
Celli,J., Duijf,P., Hamel,B.C.J., Bamshad,M., Kramer,B., Smits,A.P.T., Newbury-Ecob,R., Hennekam,R.C.M., van-Buggenhout,G., van-Haeringen,A., Woods,C.G., von-Essen,A.J., de-Waal,R., Vriend,G., Haber,D.A., Yang,A., McKeon,F., Brunner,H.G. & van-Bokhoven,H. (1999).
Heterozygous Germline mutations in the p53 homolog p63 are the cause of EEC syndrome.. Cell, 99, 1-20
The EEC syndrome possibly gives people a series of extremely unpleasant problems suc as: Ectrodactyly, Ectodermal dysplasia (whatever those are), cleft lip, etc. It influences skin, teeth, hair and nails. It can also give lacrimal duct abnormalities, urogenital problems, conductive hearing loss, facial dysmorphism, etc. Brunner and Bokhoven found the gen that holds the mutations that lead to EEC. It was our contribution to model p63 based on p53. This was easy. High homology, and no indels anywhere near the residues of interest. The nice thing was that all five EEC causing mutations could easily be explained from the model. Four would hinder DNA binding, and one would prevent proper folding of the DNA binding domain. So, presently a screaning method is tested that is based on binding a piece of DNA.
Copley,R.R. (1999).
The gene for X-linked anhidrotic ectodermal dysplasia encodes a TNF-like domain. J Mol Med, 77, 361-363
Copley,R.R., Schultz,J., Ponting,C.P. & Bork,P. (1999).
Protein families in multicellular organisms. Curr Opin Struct Biol, 9, 408-415
Copley,R.R., Ponting,C.P. & Bork,P. (1999).
Phospholipase A and Wnt-like proteins are unlikely to share common ancestry. Curr.Biol., 9, 178-179
Dandekar,T. & Du,F. (1999).
Analyzing the interplay between secondary and tertiary structure predictions in folding simulations with a genetic
algorithm. J. of Molecular Modeling, 5, 78-89
Dandekar,T., Schuster,S., Snel,B., Huynen,M. & Bork,P. (1999).
Pathway alignment: application to the comparative analysis of glycolytic
enzymes. Biochem J , 1999, 115-124
Dupradeau,F.Y., Altenberg-Greulich,B., Warin,R.F., Fuentes,V., Monti,J.P. & Rochette,J. (1999).
A 3-D Model Building by Homology of the HFE Protein:
Molecular Consequences and Application to specific Antibodies specific for the alpha1 Domain. Blood, 94, 3204-3204
Eisenhaber,B., Bork,P. & Eisenhaber,F. (1999).
Prediction of Potential GPI-modification Sites in Proprotein Sequences. J Mol Biol, 292, 741-758
Eisenhaber,F. & Bork,P. (1999).
Valuation of human-readable annotation in biomolecular sequence databases
with biological rule libraries. Bioinformatics, 15, 528-535
Gibson,T. & Bork,P. (1999).
Sequence analysis. In: Enzyclopedia of Molecular Biology. 2320-2324
(Creighton,T.) Wiley & Son Inc., New york
Hanke,J., Lehmann,G., Bork,P. & Reich,J.G. (1999).
Associative database for protein sequences. Bioinformatics, 15, 741-748
Hanke,J., Zastrow,I., Aydin,A., Lehmann,G., Delbruck,S., Luft,F., Reich,J.G. & Bork,P. (1999).
Alternative splicing of human genes: More the rule than the exeption?. Trends Genet., 1999, 389-390
Horn,F., Mokrane,M., Weare,J. & Vriend,G. (1999).
G protein-coupled receptors, or the power of data. . Genomics and Proteomics: Functional and Computational Aspects., 1, x-x
Everything, and a little bit more, you ever wanted to know(but were too afraid to ask) about the collection and harvesting of GPCR data.
Huynen,M.A., Dandekar,T. & Bork,P. (1999).
Variation and evolution of the citric-acid cycle: a genomic perspective.. Trends Microbiol, 7, 281-291
Huynen,M.A., Snel,B. & Bork,P. (1999).
Lateral Gene Transfer, Genome Surveys and the Phylogeny of Prokaryotes. Science, 286, 1441
Keese,M.A., Saffrich,R., Dandekar,T., Becker,K. & Schirmer,R.H. (1999).
Microinjected glutathione reductase crystals as indicators of the redox status in living cells. FEBS Letters, 447, 135-138
Kelly,L., Sharma,K. & Dandekar,T. (1999).
Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity (Condensation and commentary).. Chemtracts - Biochemistry and Molecular Biology, 12, 223-228
Koenig,R. & Dandekar,T. (1999).
Refined genetic algorithm simulations to model proteins. J. Mol. Model., 5, 317-324
Koenig,R. & Dandekar,T. (1999).
Improving genetic algorithms for protein folding simulations
by systematic crossover. BioSystems, 50, 17-25
Koretke,K.K., Russell,R.B., Copley,R.R. & Lupas,A.N. (1999).
Fold Recognition Using Sequence and Secondary Structure Information. Proteins: Structure, Function and Genetics Suppl., 3, 141-148
Liu,Z., Macias,M.J., Bottomley,M.J., Stier,G., Linge,J.P., Nilges,M., Bork,P. & Sattler,M. (1999).
The 3D structure of the HRDC domain and implications for the Werner and
Bloom syndrome proteins. Structure, 7, 1557-1566
Liu,Z., Song,D., Kramer,A., Martin,A.C., Dandekar,T., Schneider-Mergener,J., Bautz,E.K. & Dubel,S. (1999).
Fine mapping of the antigen-antibody interaction of scFv215, a recombinant antibody inhibiting RNA polymerase II from Drosophila
melanogaster. J Mol Recogni, 12, 103-111
Morett,E. & Bork,P. (1999).
A novel transactivation domain in parkin. Trends Biochem Sci , 24, 229-231
Muller,S.A., Sasaki,T., Bork,P., Wolpensinger,B., Schulthess,T., Timpl,R., Engel,A. & Engel,J. (1999).
Domain Organization of Mac-2 Binding Protein and its Oligomerization to
Linear and Ring-like Structures. J Mol Biol, 291, 801-813
Musco,G., de-Tommasi,T., Stier,G., Kolmerer,B., Bottomley,M., Adinolfi,S., Muskett,F.W., Gibson,T.J., Frenkiel,T.A. & Pastore,A. (1999).
Assignment of the 1H, 15N, and 13C resonances of the C-terminal domain of frataxin, the protein responsible for Friedreich ataxia. . J. Biomol. NMR, 15, 87-88
Nagle,D.L., McGrail,S.H., Vitale,J., Woolf,E.A., Dussault,B.J., DiRocco,L., Holmgren,L., Montagno,J., Bork,P., Huszar,D., Fairchild-Huntress,V., Ge,P., Keilty,J., Ebeling,C., Baldini,L., Gilchrist,J., Burn,P., Carlson,G.A. & Moore,K.J. (1999).
The mahogany protein is a receptor involved in suppression of obesity. Nature, 398, 148-152
Nickel,R., Ott,C., Dandekar,T. & Leippe,M. (1999).
Pore-forming peptides of Entamoeba dispar Similarity and divergence to amoebapores in structure, expression and activity.. Eur J Biochem, 265, 1002-1007
Nielsen,J.E., Andersen,K.V., Borchert,T.V. & Vriend,G. (1999).
Determinants of Bacillus alpha-Amylase pH-Activity Profiles. Protein Science, 8, 75-75
This was a poster abstract
Nielsen,J.E., Andersen,K.V., Honig,B., Hooft,R.W., Klebe,G., Vriend,G. & Wade,R.C. (1999).
Improving macromolecular electrostatics calculations.. Prot.Eng. , 12, 657-662
Nielsen,J.E., Beier,L., Otzen,D., von-Borchert,T., Frantzen,H.B., Andersen,K.V. & Svendsen,A. (1999).
Electrostatics in the active site of an alpha-amylase. Eur J Biochem, 264, 816-824
Ponting,C.P., Bork,P., Schultz,J. & Aravind,L. (1999).
No Sec7-homology domain in guanine-nucleotide-exchange factors that act on ras and Rho. Trends Biochem Sci, 24, 177-178
Ponting,C.P., Aravind,L., Schultz,J., Bork,P. & Koonin,E.V. (1999).
Eukaryotic Signalling Domain Homologues in Archaea and Bacteria. Ancient Ancestry and Horizontal Gene Transfer.. J Mol Biol , 289, 729-745
Ponting,C.P., Hofmann,K. & Bork,P. (1999).
A latrophilin/CL-1-like GPS domain in polycystin-1. Curr Biol, 9, 585-588
Ponting,CP., Schultz,J., Milpetz,F. & Bork,P. (1999).
SMART: identification and annotation of domains from signalling and extracellular protein sequences. Nucleic Acids Res, 27, 229-232
Schuster,S., Dandekar,T. & Fell,D.A. (1999).
Detection of elementary flux modes in biochemical networks:
A pronising tool for pathway analysis and metabolic
engineering. Trends in Biotechnology, 17, 53-60
Smalla,M., Schmieder,P., Kelly,M., TerLaak,A., Krause,G., Ball,L., Wahl,M., Bork,P. & Oschkinat,H. (1999).
Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites. Protein Sci., 8, 1954-1961
Snel,B., Bork,P. & Huynen,M.A. (1999).
Genome phylogeny based on gene content. Nature Genet, 21, 108-110
Struttmann,T., Fabro,M., Romieu,G., de-Roquefeuil,G., Touchon,J., Dandekar,T. & Ritchie,K. (1999).
Quality-of-life assessment in the old using the WHOQOL 100: differences
between patients with senile dementia and patients with cancer.. Int Psychogeriatrics, 11, 273-9
Sunyaev,S., Eisenhabe,F., Rodchenkov,I., Eisenhaber,B., Tumanyan,V. & Kuznetsov,E. (1999).
PSIC: Profile extraction from sequence alignments with position-specific counts of independent observations.. Protein Engineering, 12, 387-394
Sunyaev,S., Hanke,J., Aydin,A., Wirkner,U., Zastrow,I., Reich,J. & Bork,P. (1999).
Prediction of nonsynonymous single nucleotide polymorphisms in human disease-associated genes. J.Mol.Med., 77, 754-760
Vriend,G., Berendsen,H.J.C., van-den-Burg,B., Venema,G. & Eijsink,V.G.H. (1999).
Early steps in the unfolding of thermolysin-like proteases. J.Biol.Chem, 273, 35074-35077
The thermolysine like protease from bacillus stearothermophilus has its T50 at around 70
degrees. The stability is limited by one single loop around calcium III (roughly loop 50-70)
that unfolds and gets cleaved long before the reversible global unfolding can take place. We
have eliminated this week link by mutagenesis in many different ways, but never before did
we provide such elegant evidence for the idea that local unfolding is critical.
In this study we engineered a second week link. This new molecule can now be stabilized by
mutations in either of the two early unfolding regions, but non of the mutations shows a
strong stabilization because if one of the two loops is rendered autolytically insusceptible, the
other loop takes over. Mutations in both loops at the same time, however, do create stability.
A mathematical model is derived that is based on two local unfolding pathways and the
experimental data is shown to beautifully fit in this model.
Weare,J. & Vriend,G. (1999).
Web WHAT IF: Integrating WHAT IF and the WWW. Protein Science, 8, 47-47
This was a poster abstract
Willassen,N.P., Rodriguez,R. & Vriend,G. (1999).
An information system for "low-complexity sequence regions". Protein Science, 8, 47-47
This was a poster abstract
Williams,J.C., Zeelen,J.P., Neubauer,G., Vriend,G., Backmann,J., Michels,P.A.M., Lambeir,A.M. & Wierenga,R.K. (1999).
Structural and mutagenesis studies of leishmania triosephosphate isomerase: a point mutant can
convert a mesophilic enzyme into a superstable enzyme without losing catalytic power.. Prot.Eng. , 12, 243-250
A Glu on the dimer interface of TIM is not very happy. It has to be protonated to sit there at all. This protonation costs a lot of energy (we are working on a computational estimate of how much it costs). Mutating it to Gln (which is at that position in many other TIMs, makes the thing darn stable.
Zeller,R., Haramis,A.G., Zuniga,A., McGuigan,C., Dono,R., Davidson,G., Chabanis,S. & Gibson,T. (1999).
Formin defines a large family of morphoregulatory genes and functions in establishment of the polarising region.. Cell Tissue Res., 296, 85-93
de-Groot,B.L., Vriend,G. & Berendsen,H.J.C. (1999).
Conformational changes in the chaperonin GRoEL: New insights into the allosteric mechanism. J.Mol.Biol, 286, 1241-1249
Using the CONCOORD method we were able to generate a molecular dynamics trajectory
equivalent to a few nanoseconds for this whole (massively big; almost 10000 residues!)
chaperonin. This analysis confirmed several earlier speculations about atomic communication
between the two half molecules.
van-Nimwegen,E., Crutchfield,J.P. & Huynen,M.A. (1999).
Neutral evolution of mutational robustness. Proc Natl Acad Sci U S A, 96, 9716-9720
Andrade,M.A. & Valencia,A. (1998).
Automatic extraction of keywords from scientific text: application to the knowledge domain of protein families. Bioinformatics, 14, 600-607
Abstract web server - additional information
Bansal,A.K., Bork,P. & Stuckey,P. (1998).
Automated Pair-wise Comparisons of Microbial Genomes. Mathematical Modelling and Scientific Computing, 9, 1-23
Beckmann,G., Hanke,J., Bork,P. & Reich,J. (1998).
Merging domains: Fold prediction for laminin G-like and aminoterminal thrombospondin-like modules based on homology to pentraxins. J.Mol.Biol., 275, 725-730
Bork,P. & Eisenberg,D. (1998).
Deriving biological knowledge from genomic sequence. Curr.Opin.Struct.Biol., 8, 331-332
(editorial)
Bork,P. & Koonin,E.V. (1998).
Predicting function from protein sequences: Where are the bottlenecks?. Nature Genet., 18, 313-318
Bork,P., Dandekar,T., Diaz-Lazcoz,Y., Eisenhaber,F., Huynen,M.A. & Yuan,Y.P. (1998).
Predicting function: From genes to genomes and back. J.Mol.Biol., 283, 707-725
Abstract Full article (PDF 2089K)
Bork,P., Dandekar,T., Eisenhaber,F. & Huynen,M.A. (1998).
Glycogen-binding domains in protein phosphatases. J.Mol.Med., 76, 77-79
Botquin,V., Hess,H., Fuhrmann,G., Anastassiadis,C., Gross,M.K., Vriend,G. & Scholer,H.R. (1998).
New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2.. Genes Dev, 12, 2073-2090
The POU transcription factor Oct-4 is expressed specifically in the germ line, pluripotent cells of the pregastrulation embryo and stem cell lines derived from the early embryo. Osteopontin (OPN) is a protein secreted by cells of the preimplantation embryo and contains a GRGDS motif that can bind to specific integrin subtypes and modulate cell adhesion/migration. We show that Oct-4 and OPN are coexpressed in the preimplantation mouse embryo and during differentiation of embryonal cell lines. Immunoprecipitation of the first intron of OPN (i-opn) from covalently fixed chromatin of embryonal stem cells by Oct-4-specific antibodies indicates that Oct-4 binds to this fragment in vivo. The i-opn fragment functions as an enhancer in cell lines that resemble cells of the preimplantation embryo. Furthermore, it contains a novel palindromic Oct factor recognition element (PORE) that is composed of an inverted pair of homeodomain-binding sites separated by exactly 5 bp (ATTTG +5 CAAAT). POU proteins can homo- and heterodimerize on the PORE in a configuration that has not been described previously. Strong transcriptional activation of the OPN element requires an intact PORE. In contrast, the canonical octamer overlapping with the downstream half of the PORE is not essential. Sox-2 is a transcription factor that contains an HMG box and is coexpressed with Oct-4 in the early mouse embryo. Sox-2 represses Oct-4 mediated activation of i-opn by way of a canonical Sox element that is located close to the PORE. Repression depends on a carboxy-terminal region of Sox-2 that is outside of the HMG box. Expression, DNA binding, and transactivation data are consistent with the hypothesis that OPN expression is regulated by Oct-4 and Sox-2 in preimplantation development.
Brown,N.P., Sander,C. & Bork,P. (1998).
Frame: detection of genomic sequencing errors.. Bioinformatics, 14-4, 367-371
Cai,Y. & Bork,P. (1998).
Homology-based gene prediction using neural nets. Analytical Biochemistry , 265, 269-74
Chenna,R. (1998).
Generating Dynamic Documents From Templates . Digital Systems Report, Summer, 14-19
Dandekar,T. & Argos,P. (1998).
Structural Basis for the Binding of a Globular Antifreeze Protein to Ice (Review). Chemtracts - Biochemistry and Molecular Biology, 11, 229-232
Dandekar,T. & Argos,P. (1998).
Determination of the Fold of the Core Protein of Hepatitis B Virus by Electron Cryomicroscopy (Review). Chemtracts - Biochemistry and Molecular Biology, 11, 161-165
Dandekar,T. & Sharma,K. (1998).
Regulatory RNA. In: Regulatory RNA. 1-262
( Hardcover, ISBN 3-540-64343-5) Springer Verlag, Heidelberg, Germany
Dandekar,T., Snel,B., Huynen,M.A. & Bork,P. (1998).
conservation of gene order: a fingerprint of proteins that physically interact. TIBS, 23, 324-328
Dandekar,T., Beyer,K., Bork,P., Kenealy,M.R., Pantopoulos,K., Hentze,M., Sonntag-Buck,V., Flouriot,G., Gannon,F. & Schreiber,S. (1998).
Systematic genomic screening and analysis of mRNA in untranslated regions
and mRNA precursors: combining experimental and computational
approaches.. Bioinformatics, 14-3, 271-278
Doerks,T., Bairoch,A. & Bork,P. (1998).
Protein annotation: detective work for function prediction. Trends Genet., 14, 248-250
Eisenhaber,B., Bork,P. & Eisenhaber,F. (1998).
Sequence properties of GPI-anchored proteins near the omega-site: constraints for the polypeptide binding site of the putative transamidase. Protein Engineering, 11, 1155-1161
Glycosylphosphatidylinositol (GPI) anchoring is a common post-translational modification of
extracellular eukaryotic proteins. Attachment of the GPI moiety to the carboxyl terminus (omega-site)
of the polypeptide occurs after proteolytic cleavage of a C-terminal propeptide. In this work, the
sequence pattern for GPI-modification was analyzed in terms of physical amino acid properties based on
a database analysis of annotated proprotein sequences. In addition, to a refinement of previously
described sequence signals, we report conserved sequence properties in the regions omega - 11...omega -
1 and omega + 4...omega + 5. We present statistical evidence for volume-compensating residue
exchanges with respect to the positions omega - 1...omega + 2. Differences between protozoan and
metazoan GPI-modification motifs consist mainly in variations of preferences to amino acid types at the
positions near the omega-site and in the overall motif length. The variations of polypeptide substrates
are exploited to suggest a model of the polypeptide binding site of the putative transamidase, the enzyme
catalyzing the GPI-modification. The volume of the active site cleft accommodating the four residues
omega - 1...omega + 2 appears to be 540 Å3.
Eisenhaber,F. & Bork,P. (1998).
Sequence and Structure of Proteins. In: Recombinant proteins, monoclonal antibodies and theraeutic genes (series Biotechnology, 2nd. Edition). 5, 43-86
(Rehm, H.-J. Reed, G) Wiley-VCH Weinheim
Eisenhaber,F. & Bork,P. (1998).
Wanted: subcellular localization of proteins based on sequence. Trends in Cell Biology, 8, 169-170
Eisenhaber,F. (1998).
Stops Genejockeys being taken for a ride. Trends in Cell Biology, 8, 377-378
Gibson,T.J. & Spring,J. (1998).
Genetic redundancy in vertebrates: polyploidy and persistence of genes encoding multidomain proteins. Trends Genet, 14, 46-49
Gibson,T.J., Chenna,R., Gemuend,C. & Aasland,R. (1998).
The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor.. Trends Biochem. Sci., 23, 242-244
Heinrich,R. & Schuster,S. (1998).
The modelling of metabolic systems. Structure, control and optimality. BioSystems, 47, 61-77
Hofacker,I.L., Fekete,M., Flamm,C., Huynen,M.A., Rauscher,S., Stolorz,P. & Stadler,P. (1998).
Automatic detection of conserved RNA structure elements in complete RNA virus genomes.. Nucl. Acids Res., 26, 3825-3836
Hooft,R.W.W. & Vriend,G. (1998).
Some WHAT_CHECK checks explained. PDB Newsletter, 4, 1-10
In this short note we explain the cell dimension check option in WHAT_CHECK. The
full text is available.
Horn,F. & Vriend,G. (1998).
G protein-coupled receptors in silico. J Mol Med, 76, 464-468
Horn,F., Weare,J., Beukers,M.W., Hoersch,S., Bairoch,A., Chen,W., Edvardsen,O., Campagne,F. & Vriend,G. (1998).
GPCRDB: an information system for G protein coupled receptors. Nucleic Acids Res, 26, 277-281
This is the first 'official' GPCRDB article. It does not provide much
science, but should be seen as a road map for GPCRDB navigation.
Horn,F., Bywater,R., Krause,G., Kuipers,W., Oliveira,L., Paiva,A.C., Sander,C. & Vriend,G. (1998).
The interaction of class B G protein-coupled receptors with their hormones.. Receptors Channels, 5, 305-314
In common with many G protein-coupled receptors, dysfunction in members of the Class B or glucagon-like receptors can elicit a wide spectrum of disease related activities. Consequently, they are potential targets in many different areas of pharmacological research. Unlike the class A or rhodopsin-like receptors, for which at least some structural similarity to bacteriorhodopsin has been detected, absolutely no structural information is available for the Class B G protein-coupled receptors. We present a computational study that exploits the experimental work performed by evolution to indicate residues that are potentially involved in ligand binding in the Class B G protein-coupled receptors. We perform an analysis of mutations that occurred in a correlated fashion between the receptors and their peptidic ligands. The inference that the residues detected in this manner are involved in a direct interaction between the receptor and the ligand is in good agreement with the mutation studies that have already been published.
Huynen,M.A. & Bork,P. (1998).
Measuring genome evolution. PNAS, 95, 5849-5856
Abstract, Full Text, PDF Download
Huynen,M.A. & van-Nimwegen,E. (1998).
The frequency distribution of gene family sizes in complete genomes.. Mol Biol Evol, 1998, 583-9
Huynen,M.A., Dandekar,T. & Bork,P. (1998).
Differential genome analysis applied to the species-specific features of Helicobacter pylori. FEBS Letters, 426, 1-5
Huynen,M.A., Doerks,T., Eisenhaber,F., Orengo,C., Sunyaev,S.R., Yuan,Y.P. & Bork,P. (1998).
Homology-based fold predictions for Mycoplasma genitalium proteins. J.Mol.Biol., 280, 323-326
Jacobs,T., Bruchhaus,I., Dandekar,T., Tannich,E. & Leippe,M. (1998).
Isolation and molecular characterization of a surface-bound proteinase of Entamoeba histolytica.. Mol Microbiol, 27, 269-276
Jeanmougin,F., Thompson,J.D., Gibson,T.J., Gouy,M. & Higgins,D.G. (1998).
Multiple sequence alignment with Clustal X.. Trends Biochem. Sci., 23, 403-405
Kamlowski,A., Altenberg-Greulich,B., Van-der-Est,A., Zech,S.G., Bittl,R., Fromme,P., Lubitz,W. & Stehlik,D. (1998).
The Quinone Acceptor A1 in Photosystem I: Binding Site, and Comparison to QA in Purple Bacteria Reaction Centers. The Journal of Physical Chemistry B, 102, 8278-8287
The nature of the binding site of the quinone acceptor A1 in Phototsystem I (PSI) is studied by modeling the protein and cofactor on the basis of structural data derived from the intermediate resolution 4 A X-ray diffraction electron densitiy map, the position and orientation of A1 as evaluated from EPR data, and the histidine ligation of P700 as deduced from mutation experiments. Several models are constructed within the dgrees of freedom allowed by the experimental constraints.
Kharrat,A., Millevoi,S., Baraldi,E., Ponting,CP., Bork,P. & Pastore,A. (1998).
Conformational stability studies of the pleckstrin DEP domain: definition of the domain boundaries.. Biochim Biophys Acta, 1385, 157-164
Kholodenko,B.N., Schuster,S., Garcia,J., Westerhoff,H.V. & Cascante,M. (1998).
Control analysis of metabolic systems involving quasi-equilibrium reactions. Biochim. Biophys. Acta, 1379, 337-352
Lock,P., Abram,C.L., Gibson,T. & Courtneidge,S.A. (1998).
A new method for isolating tyrosine kinase substrates used to identify Fish, an SH3 and PX domain-containing protein, and Src substrate.. EMBO J., 17, 4346-4357
Marhl,M., Schuster,S. & Brumen,M. (1998).
Mitochondria as an Important Factor in the Regulation of Amplitudes of Cytosolic Calcium Oscillations. Biophys. Chem., 71, 125-132
Mohr,E., Horn,F., Janody,F., Sanchez,C., Pillet,V., Bellon,B., Roder,L. & Jacq,B. (1998).
FlyNets and GIF-DB, two internet databases for molecular interactions in Drosophila melanogaster. Nucleic Acids Res, 26, 89-93
During her stay in Heidelberg Florence worked a bit more on her PhD
project to get things finished nicely and to leave no loose ends. This
article is the result of that work.
Morett,E. & Bork,P. (1998).
Evolution of new protein function: recombinational enhancer Fis originated by horizontal gene transfer from the transcriptional regulator NtrC. FEBS Lett., 433, 108-112
Petfalski,E., Dandekar,T., Henry,Y. & Tollervey,D. (1998).
Processing of the precursors to small nucleolar RNAs and rRNAs requires common components. Mol Cell Biol, 18, 1181-1189
Rodriguez,R., Chinea,G., Lopez,N., Pons,T. & Vriend,G. (1998).
Homology modeling, model and software evaluation: three related resources.. Bioinformatics, 14, 523-528
Motivation : Homology modeling is rapidly becoming the method of choice for obtaining three-dimensional coordinates for proteins because genome projects produce sequences at a much higher rate than NMR and X-ray laboratories can solve the three-dimensional structures. The quality of protein models will not be immediately clear to novices and support with the evaluation seems to be needed. Expert users are sometimes interested in evaluating the quality of modeling programs rather than the quality of the models themselves. Results : Three servers have been made available to the scientific community: a homology modeling server, a model quality evaluation server and a server that evaluates models built of proteins for which the structure is already known, thereby implicitly evaluating the quality of the modeling program. Availability : The modeling-related servers and several structure analysis servers are freely available at http://swift.embl-heidelberg.de/serve
Schultz,J., Milpetz,F., Bork,P. & Ponting,C.P. (1998).
SMART, a simple modular architecture research tool: Identification of signaling domains. PNAS, 95, 5857-5864
Abstract, Full Text, PDF Download
Schuster,S., Fell,D.A., Pfeiffer,T., Dandekar,T. & Bork,P. (1998).
Elementary Modes Analysis Illustrated with Human Red Cell Metabolism. In: BioThermoKinetics in the Post Genomic Era. 332-339
(C. Larsson, I.-L. Pahlman and L. Gustafsson, eds.) Chalmers,
Goeteborg
Schuster,S., Marhl,M., Brumen,M. & Heinrich,R. (1998).
Influence of Calcium Binding to Proteins on Calcium Oscillations and ER Membrane Potential Oscillations. A Mathematical Model. In: Information Processing in Cells and Tissues. 137-150
(R. Paton and M. Holcombe) Plenum Press, New York
Schuster,S., Ouhabi,R., Rigoulet,M. & Mazat,J.P. (1998).
Modelling the interrelation between the transmembrane potential and pH difference across membranes with electrogenic proton transport upon build-up of the proton-motive force. Bioelectrochem. Bioenerget., 45, 181-192
Schwirzke,M., Gnirke,A., Bork,P., Tarin,D. & Weidle,U.H. (1998).
Differential gene expression in mammary carcinoma cell lines: identification of DRIM, a new gene down-regulated in metastasis.. Anticancer Res, 18.3, 1409-1421
Steinberger,D., Vriend,G., Mulliken,J.B. & Muller,U. (1998).
The mutations in FGFR2-associated craniosynostoses are clustered in five structural elements of immunoglobulin-like domain III of the receptor.. Hum Genet, 102, 145-150
Exons 5 and 7 of the fibroblast growth factor receptor 2 (FGFR2) gene code for immunoglobulin-like domain III (IgIII) and for the region connecting the second and the third Ig domain of the receptor. Numerous mutations in these two exons have been shown to cause various craniosynostotic syndromes. Here, we describe three previously unrecognized mutations at amino acid positions 276, 301, and 314, in one nonspecific craniosynostosis and in two Crouzon patients. We also present a polypeptide model of IgIII of FGFR2. The known mutations involve five distinct structural elements of the receptor. The changes within these elements affect receptor function by various mechanisms, including altered dimerization, truncation, increased mobility between Ig domains, disintegration of IgIII, and alteration of the ligand-binding site.
Sunyaev,S.R., Eisenhaber,F., Argos,P., Kuznetsov,E.N. & Tumanyan,V.G. (1998).
Are knowledge-based potentials derived from protein strucure sets are discriminative with respect to amino acid types ?. Proteins, 31, 323-326
Trelles,O., Andrade,M.A., Valencia,A., Zapata,E.L. & Carazo,J.M. (1998).
Computational space reduction and parallelization of a new clustering approach for large groups of sequences. Bioinformatics, 14, 439-451
Van-den-Burg,B., Eijsink,V.G., Vriend,G., Veltman,O.R. & Venema,G. (1998).
Rendering one autolysis site in Bacillus subtilis neutral protease resistant to cleavage reveals a new fission.. Biotechnol Appl Biochem , 27, 125-132
Autolytic degradation of the thermolysin-like proteinase of Bacillus subtilis (TLP-sub) is responsible for the irreversible inactivation of the enzyme at elevated temperatures. Previously we have reported five cleavage sites in TLP-sub [Van den Burg et al. (1990) Biochem. J. 272, 93-97]. In an attempt to render the enzyme less susceptible to autolytic breakdown, one of the fission sites, located between Leu-156 and Ile-157, was modified by replacing Ile-157, C-terminally located with respect to the fission site, by an Asp residue. Aspartic acid is less preferred at this position with respect to the substrate preference of TLP-sub. Modelling studies indicated that this mutation was unlikely to cause conformational changes in the enzyme. Although the 156-157 fission was not observed in the mutant enzyme, a new fission site, between Gly-148 and Val-149, was now observed.
VandenBurg,B., Vriend,G., Veltman,O.R., Venema,G. & Eijsink,V.G.H. (1998).
Engineering an enzyme to resist boiling. PNAS, 95, 2056-2060
This is one of the tops in the neutral protease roler coaster ride. Here we actually
combined most of the knowledge we gathered in the articles listed above and managed
to make one of the neutral proteases boilable. See also the commentary in the same
volume of PNAS:
Frances H. Arnold Enzyme engineering reaches the boiling point PNAS 1998 95:
2035-2036. The text of this press-release looks like:
Article Highlights
Veltman,O.R., Vriend,G., Berendsen,H.J., Van-den-Burg,B., Venema,G. & Eijsink,V.G. (1998).
A single calcium binding site is crucial for the calcium-dependent thermal stability of thermolysin-like proteases.. Biochemistry, 37, 5312-5319
Thermostable thermolysin-like proteases (TLPs), such as the TLP of Bacillus stearothermophilus CU-21 (TLP-ste), bind calcium in one double (Ca1,2) and two single (Ca3, Ca4) calcium binding sites. The single sites are absent in thermolabile TLPs, suggesting that they are determinants of (variation in) TLP stability. Mutations in the Ca3 and Ca4 sites of TLP-ste indeed reduced thermal stability, but only mutations in the Ca3 site affected the calcium-dependence of stability. The predominant effect of the Ca3 site results from the fact that the Ca3 site is part of a region of TLP-ste, which unfolding is crucial for thermal inactivation. Thermal inactivation is not caused by the absence of calcium from the Ca3 site per se, but rather by unfolding of a region of TLP-ste for which stability depends on the occupancy of the Ca3 site. In accordance with this concept is the observation that the effects of mutations in the Ca3 site could be compensated by stabilizing mutations near this site. In addition, it was observed that the contribution of calcium binding to the Ca3 was substantially reduced in extremely stable TLP-ste variants containing multiple stabilizing mutations in the Ca3 region. Apparently, in these latter variants, unfolding of the Ca3 region contributes little to the overall process of thermal inactivation.
Veltman,O.R., Eijsink,V.G.H., Vriend,G., DeKreij,A., Venema,G. & VandenBurg,B. (1998).
Probing catalytic hinge bending motions in thermolysin-like proteases by Glycine -> Alanine mutations. Biochemistry, 1, 1-10
Molecular dynamics are an essential aspect of the activity of neutral proteases. It was
suggested by Holland et al., based on structure comparisons that a hinge bending motion
that leads to opening and closing (a little bit) of the active site mouth is essential for
activity. It seemed a sure bet that Glycine residues play a pivotal role by accomodating
this mobility. We therefore mutated some of the suspicious Glycines and also some
seemingly 'useless' Glycines as a control experiment. It looks like we could
experimentally validate Holland's ideas. Our data at least does not contradict Holland's
ideas.
Willeke,F., Ridder,R., Bork,P., Klaes,R., Mechtersheimer,G., Schwarzbach,M., Zimmer,D., Kloor,M., Lehnert,T., Herfarth,C. & vonKnebel-Doeberitz,M. (1998).
Identical variant TSG101 transcripts in soft tissue sarcomas and various non-neoplastic tissues. Mol Carcinog, 23, 195-200
Wilson,K., Sander,C., Hooft,R.W.W. & Vriend,G. (1998).
Who checks the checkers? Four validation tools applied to eight atomic resolution structures.. J.Mol.Biol, 276, 417-436
Validating protein structures (and models) is one of our hobbies. This article (which has
20 authors, the whole validation consortium is on it...) describes the results of validating
some structures solved at atomic resolution (around 1.0 A) that thus were supposed to
be guaranteed correct. This study revealed some problems in the ultra highly refined
structures and some problems in the refinement programs. The general conclusion
should be that the validation programs are actually working very well, and that remarks
by some crystallographers that "these validation programs give very many false
positives" really are not supported by the results of this study.
Yuan,Y.P., Eulenstein,O., Vingron,M. & Bork,P. (1998).
Towards detection of orthologues in sequence databases.. Bioinformatics, 14, 285-289
Zheng,Z.M., Huynen,M.A. & Baker,C.C. (1998).
A pyrimidine-rich exonic splicing suppressor binds multiple RNA splicing factors and inhibits spliceosome
assembly.. Proc Natl Acad Sci U S A, 95, 14088-93
Beyer,K., Dandekar,T. & Keller,W. (1997).
RNA-ligands selected by cleavage stimulation factor (CstF) contain distinct sequence motifs that function as downstream elements in 3'-end processing of pre-mRNA. J. Biol. Chemistry, 272, 26769-26779
Bork,P. (1997).
Comparative genome analysis::From sequences to functions. Developments in Industrial Mircobiol., 34, 21-23
Bork,P. (1997).
Bioinformatics and molecular medicine - introduction and call for papers. J. Mol.Med., 75, 3-4
Bork,P., Schultz,J. & Ponting,C.P. (1997).
Cytoplasmic signalling domains: the next generation. TIBS, 22, 296-298
Bork,P., Altschul,S.F., Bucher,P., Hofmann,K., Neuwald,A. & Koonin,E.V. (1997).
A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. FASEB J., 11, 68-76
Cai,Y., Yu,H. & Chou,K.C. (1997).
Artificial neural network method for predicting the specificity of GalNAc-transferase. J. Protein Chem., 16, 689-700
Carugo,O. & Eisenhaber,F. (1997).
Probabilistic evaluation of similarity between pairs of three-dimensional structures utilizing temperature factors. Journal of Applied Crystallography, 1997, 547-549
Dandekar,T. & Argos,P. (1997).
Applying experimental data to protein fold prediction with the genetic algorithm. Protein Engineering, 10, 877-893
Dandekar,T. & Koenig,R. (1997).
Computational methods for the prediction of protein folds. Biochimica et Biophysica Acta, 1343, 1-15
Dandekar,T. & Leippe,M. (1997).
Molecular modelling of amoebapore and NK-lysin: A common structure for cytolytic effector molecules of most distantly related organisms. Folding & Design, 2, 47-52
Dandekar,T. (1997).
Improving protein structure prediction by new strategies, experimental insights and the genetic algorithm. J. Mol. Modeling, 3, 312-314
Dandekar,T. (1997).
Free radicals and memory loss. Redox Report, 3, 71-73
Frigerio,F., Vriend,G. & Eijsink,V.G.H. (1997).
Model building by mutagenesis. Prot. Eng., 10, 223-230
The present study concerns the use of site-directed mutagenesis experiments to optimize a three-dimensional model of the neutral protease of Bacillus subtilis (NP-sub). An initial model of NP-sub was constructed using the crystal structures of the homologous neutral proteases of Bacillus thermoproteolyticus (thermolysin) and Bacillus cereus as templates. The largest portion of NP-sub could be modelled satisfactorily, using standard techniques, but several surface-located regions could only be modelled with a high degree of uncertainty. In order to make the model more reliable in these regions a "model building by mutagenesis' approach was adopted. Mutations were designed such that their effect on thermal stability could indicate how their local environment should be modelled. This approach provided insight in the local structure of several regions in NP-sub that were hard to model on the basis of homology with the two known structures alone.
Gorlich,D., Dabrowski,M., Bischoff,F.R., Kutay,U., Bork,P., Hartmann,E., Prehn,S. & Izaurralde,E. (1997).
A novel class of RanGTP-binding proteins. J.Cell.Biol., 138, 65-80
Greene,L.A., Henikoff,S., Pietrokovski,S., Bork,P., Attwood,T., Hood,L. & Bairoch,A. (1997).
Building gene families: Genome maps VIII. Science, 278, 615-630
Suppl. (poster)
Hegyi,H. & Bork,P. (1997).
On the classification and evolution of protein modules . J.Prot.Chem., 16, 545-551
Hegyi,H., Lai,J.M. & Bork,P. (1997).
The Sequence Alerting Server--a new WEB server. Comput Appl Biosci, 13, 619-620
Henikoff,S., Greene,L.A., Pietrokovski,S., Bork,P., Attwood,T. & Hood,L. (1997).
Gene families: the taxonomy of protein paralogs and chimeras. Science, 278, 609-614
Hooft,R.W.W., Sander,C. & Vriend,G. (1997).
Objectively judging the quality of a protein structure from a Ramachandran plot. CABIOS, 13, 425-430
This paper describes a statistical means of calculating an objective score from a Ramachandran plot, taking the differences between residue types into account.
Huynen,M.A., Diaz-Lazcoz,Y. & Bork,P. (1997).
Differential genome display. Trends Genet., 13, 389-390
Huynen,M.A., Guttel,R. & Konings,D.A.M. (1997).
Assessing the reliability of RNA folding using statistical mechanics. Journal of Molecular Biology, 267, 1104-1112
Kuipers,W., Oliveira,L., Vriend,G. & Ijzerman,A.P. (1997).
Identification of class-determining residues in G protein-coupled receptors by sequence analysis. Receptors Channels, 5, 159-174
G protein-coupled receptors (GPCRs) form a large superfamily of receptors that are characterised by a seven transmembrane helical motif. The functions they perform, such as binding ligands and G proteins, are related to the presence of certain amino acids in critical positions. We have developed a computational sequence pattern correlation technique for the recognition of such function-determining residues. The method searches for residues that are conserved in one class of proteins with a certain function but are different in other classes. The basic idea is that such residues are probably involved in this particular function. This technique was used to find residues that play a role in the binding of endogenous as well as exogenous ligands to various receptors. Many of the residues that were detected have been experimentally determined as important for ligand binding. More importantly, however, we also detected residues that are interesting targets for future mutation studies aimed at elucidating the sequence-function relationship in GPCRs. The information obtained may help improve three-dimensional GPCR models and can be useful for the study of receptor-ligand interactions.
Mansfeld,J., Vriend,G., Dijkstra,B.W., Veltman,O.R., VandenBurg,B., Venema,G., Ulbrich-Hofmann,R. & Eijsink,V.G. (1997).
Extreme stabilization of a thermolysin-like protease by an engineered disulfide bond. J Biol Chem, 272, 11152-11156
he thermal inactivation of broad specificity proteases such as thermolysin and subtilisin is initiated by partial unfolding processes that render the enzyme susceptible to autolysis. Previous studies have revealed that a surface-located region in the N-terminal domain of the thermolysin-like protease produced by Bacillus stearothermophilus is crucial for thermal stability. In this region a disulfide bridge between residues 8 and 60 was designed by molecular modelling, and the corresponding single and double cysteine mutants were constructed. The disulfide bridge was spontaneously formed in vivo and resulted in a drastic stabilization of the enzyme. This stabilization presents one of the very few examples of successful stabilization of a broad specificity protease by a designed disulfide bond. We propose that the success of the present stabilization strategy is the result of the localization and mutation of an area of the molecule involved in the partial unfolding processes that determine thermal stability.
Morozov,V.M., Mushegian,A.R., Koonin,E.V. & Bork,P. (1997).
A putative nucleotide acid-binding domain in Werner's and Bloom's syndrome helicases. TIBS, 22, 417-418
Musco,G., Kharrat,A., Stier,G., Fraternali,F., Gibson,T.J., Nilges,M. & Pastore,A. (1997).
The solution structure of the first KH domain of the first KH domain of FMR1, the protein responsible for the fragile X syndrome. Nature Structure Biol., 4, 712-716
Mushegian,A.R., Bassett,D.E.JR., Boguski,M.S., Bork,P. & Koonin,E.V. (1997).
Positionally cloned human disease genes: patterns of evolutionary conservation and new functional motifs. PNAS., 94, 5831-5836
Ponting,C.P., Cai,Y. & Bork,P. (1997).
The breast cancer gene product TSG101: A regulator of ubiquitination?. J.Mol.Med., 75, 467-469
Ponting,C.P., Schultz,J. & Bork,P. (1997).
The signalling domain repertoire. TIBS, 22, xx-xx
Suppl. C04 (poster)
Ponting,C.P., Schultz,J. & Bork,P. (1997).
SPRY domains in ryanodine receptors (Ca-release channels). TIBS, 22, 193-194
Rodriguez,R. & Vriend,G. (1997).
Professional gambling.. Proceedings of the NATO Advanced Study Institute on Biomolecular Structure and Dynamics: Recent Experimental and Theoretical Advances., 1, 1-10
This is a review on almost all aspects of model building by homology that seemed important in late 1996. The text is based on a review that is available on the WWW based review will occasionally be updated.
Saxena,P., Whang,I., Voziyanov,Y., Harkey,C., Argos,P., Jayaram,M. & Dandekar,T. (1997).
Probing Flp: a new approach to analyze the structure of a DNA recognizing protein by combining the genetic algorithm, mutagenesis and non-canonical DNA target sites. Biochimica et Biophysica Acta, 1340, 187-204
Schultz,J., Ponting,C. & Bork,P. (1997).
SAM as a protein interaction domain in developmental regulation. Prot.Sci., 6, 249-253
Sobolev,V., Moallem,T.M., Wade,RC., Vriend,G. & Edelman,M. (1997).
CASP2 molecular docking predictions with the LIGIN software.. Proteins , 1, 210-214
Seven docking predictions were made with the LIGIN program. In six cases the location of the binding pocket was identified correctly by systematically docking everywhere within the protein structure. In two cases the ligand was docked to within 1.8 A RMSD of the experimentally determined structure. LIGIN has not been optimized to deal with highly flexible ligands that dock at the surface of proteins. Consequently, in three cases the exposed part of the ligand was docked poorly, although the buried parts were docked well, and made similar atomic contacts with the protein as in the experimentally determined structure.
Thompson,J.D., Gibson,T.J., Plewniak,F., Jeanmougin,F. & Higgins,D.G. (1997).
The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res, 25, 4876-4882
VandenBurg,B., Eijsink,V.G.H., Vriend,G., Veltman,O.R. & Venema,G. (1997).
Manipulating Bacillus neutral protease autolysis.. Prot.Eng., 10, 37-38
This is a published poster abstract for a meeting on protein engineering.
VandenBurg,B., Eijsink,V.G.H., Vriend,G., Veltman,O.R. & Venema,G. (1997).
Manipulating the autolytic pathway of a Bacillus protease.. IOS Press, 1, 1-10
This is a chapter in a book giving an overview of what we have done to alter the autolysis (and thus the stability) of neutral proteases.
Veltman,O.R., Vriend,G., Hardy,F., Mansfeld,J., VanderBurg,B., Venema,G. & Eijsink,V.G.H. (1997).
Mutational analysis of a surface area that is critical for the thermal stability of thermolysin-like proteases. EJB, 248, 433-440
We know that local unfolding processes followed by autolysis of these locally
unfolded loops are the reason for the denaturation of neutral proteases at elevated
temperatures. Therefore we have put a lot of effort into finding out which is the
loop that unfolds first because that loop is obviously the weakest link and stabilising
that loop is the only thing that really makes sense. From the other articles on this
page you can see that through the years we homed in on the area around calcium 3
in the N-terminal domain of TLP-ste as being this weakest link. In this article we
describe more than twenty mutations in the area around calcium 3. Not only does
this study confirm the importance of this area for thermal stability, the detailed
analysis also forms the basis for the production of proteases that are extremely
stable under a wide variety of experimental conditions.
Veltman,O.R., Vriend,G., VandenBurg,B., Hardy,F., Venema,G. & Eijsink,V.G. (1997).
Engineering thermolysin-like proteases whose stability is largely independent of calcium. FEBS Lett, 405, 241-244
Thermal stability of the thermolysin-like protease produced by Bacillus stearothermophilus (TLP-ste) is highly dependent on calcium at concentrations in the millimolar range. We describe the rational design and production of a fully active TLP-ste variant whose stability is only slightly dependent on calcium concentration.
Veltman,O.R., Eijsink,V.G.H., Vriend,G., Venema,G. & VandenBurg,B. (1997).
Identification of the critical calcium site in the thermolysin-like protease of B.Stearothermophilus reveals initial steps in the thermal unfolding.. Prot.Eng., 10, 39-40
This is a published poster abstract for a meeting on protein engineering.
Vincentz,M., Leite,A., Neshich,G., Vriend,G., Mattar,C., Barros,L., Weinberg,D., deAlmeida,E.R., deCarvalho,M.P., Aragao,F. & Gander,E.S. (1997).
ACGT and vicilin ciore sequences in a promotor domain required for seed-specific expression of a 2S storage protein gene are recognized by the opaque-2 regulatory protein. Plant Mol.Biol., 34, 879-889
This is an example of protein DNA interaction modelling.
Vriend,G., Hendriks,D. & Scharpe,S. (1997).
Molecular modeling of pharmaceutically important targets. Pharmaceutical enzymes, 1, 71-103
This is a review of the 1995 state of the art in modelling pharmaceutical enzymes. We
discuss modelling in general, and show some examples where we modelled
pharmaceuticcally interesting enzymes and could design inhibitors or obtain information
previously not available. We submitted this article early 1995....
Yuan,Y.P., Schultz,J., Mlodzik,M. & Bork,P. (1997).
Secreted Fringe-like signaling molecules might be glycosyltransferases. Cell, 88, 9-11
de-Freitas,S.M., de-Mello,L.V., da-Silva,M.C., Vriend,G., Neshich,G. & Ventura,M.M. (1997).
Analysis of the black-eyed pea trypsin and chymotrypsin inhibitor-alpha-chymotrypsin complex. FEBS Lett, 409, 121-127
The black-eyed pea trypsin and chymotrypsin inhibitor (BTCI) is a member of the Bowman-Birk protease inhibitor (BBI) family. The three-dimensional model of the BTCI-chymotrypsin complex was built based on the homology to Bowman-Birk inhibitors with known structures. An extensive theoretical and experimental study of these known structures has been performed. The model confirms the ideas about Bowman-Birk inhibitor structure-function relations and agrees well with our experimental data (circular dichroism, IR and light scattering). The electrostatic potentials at the enzyme-inhibitor contact surface reveal a pattern of complementary electrostatic potentials from which mutations can be inferred that could give these inhibitors an altered specificity.
deGroot,B.L., vanAalten,D.M.F., Scheek,R.M., Amadei,A., Vriend,G. & Berendsen,H.J.C. (1997).
Prediction of Protein Conformational Freedom from Distance Constraints.. PROTEINS, 29, 240-251
This article describes a method to predict potential motions in proteins. The next
article in this list describes how essential dynamics analysis can be used to filter a
molecular dynamics trajectory for thermolysin in such a way that only the low
frequency motions (correlated motions) stay alive. In this article we describe how a
random number generator can be used to prepare a set of structures, that, when
treated as MD frames can predict essential dynamics results surprisingly precise.
The method puts on all kinds of contacting atom pairs (covalently connected atoms
included) a lower and a higher distance limit and randomly shakes the molecule
(starting from random start coordinates) till all distances in the structure fall
within the given limits. Every time a solution is found, the structure is stored and
all structures together (normally about 500 structures is enough) are treated as an
MD trajectory in the essential dynamics analysis.
Several applications of the method (which Bertje called CONCOORD) can be
found in the SHAKE chapter of the WHAT IF writeup.
Aasland,R., Gibson,T.J. & Stewart,A.F. (1996).
The SANT domain: A putative DNA binding domain in the SWI-SNF and ADA complexes, the transcriptional co-repressor N-CoR and TFIIIB.. Trends Biochem Sci., 21, 87-88
Birney,E., Thompson,J.D. & Gibson,T.J. (1996).
PairWise and SearchWise: finding the optimal alignment in a simultaneous comparison of a protein profile against all DNA translation frames. Nucleic Acids Res., 24, 2730-2739
Bork,P. & Gibson,T.J. (1996).
Applying motif and profile searches. Meth.Enzym., 266, 162-184
Bork,P. & Bairoch,A. (1996).
Go hunting in sequence databases but watch out for the traps. Trends Genet., 12, 425-427
Bork,P. & Koonin,E.V. (1996).
Protein sequence motifs. Curr.Opin.Struct.Biol., 6, 366-376
Bork,P. (1996).
Sperm-egg binding protein or proto-oncogene. Science, 271, 1431-1432
Bork,P. (1996).
Von Genomsequenzen zu Proteinfunktionen . it+ti, 5, 20-26
Bork,P. (1996).
On exon shuffling and other mechanisms of domain rearrangements. Matrix Biology, 15, 311-312
Bork,P., Blomberg,N. & Nilges,M. (1996).
Internal repeats in the sequence of BRCA2. Nature Genet., 13, 22-23
Bork,P., Brown,N.P., Hegyi,H. & Schultz,J. (1996).
The protein phosphatase 2C (PP2C) superfamily: Detection of bacterial homologues. Prot.Sci., 5, 1421-1425
Bork,P., Downing,A.K., Kieffer,B. & Campbell,I.D. (1996).
Structure and distribution of modules in extracellular proteins. Quart.Rev.Biophys., 29, 119-167
Dandekar,T. & Argos,P. (1996).
Identifying the tertiary fold of small proteins with different topologies from sequence and secondary structure using the genetic algorithm and extended criteria specific for strandregions. J. Mol. Biol., 256, 645-660
Eisenhaber,F. & Argos,P. (1996).
Hydrophobic Regions on Protein Surfaces. Definition Based on Hydration Shell Structure and a Quick Method for Their Computation. Protein Engineering, 9, 1121-1133
Eisenhaber,F. (1996).
Hydrophobic Regions on Protein Surfaces. Derivation of the Solvation Energy from their Area Distribution in Crystallographic Protein Structures. Protein Science, 5, 1676-1686
Eisenhaber,F., Froemmel,C. & Argos,P. (1996).
Prediction of Secondary Structural Content of Proteins from Their Amino Acid Composition Alone. II. The Paradox with Secondary Structural Class. Proteins: Struct.Funct.Design, 25, 169-179
Eisenhaber,F., Imperiale,F., Argos,P. & Froemmel,C. (1996).
Prediction of Secondary Structural Content of Proteins from Their Amino Acid Composition Alone. I. New Analytic Vector Decomposition Methods. Proteins: Struct.Funct.Design, 24, 157-168
Gibson,T.J., Koonin,E.V., Musco,G., Pastore,A. & Bork,P. (1996).
Friedreich's ataxia protein: Phylogenetic evidence for mitochondrial disfunction. Trends Neurosci., 19, 465-468
Hanke,J., Beckmann,G., Bork,P. & Reich,J.G. (1996).
Self-organising hirarchical networks for pattern recognition in protein sequences. Prot.Sci., 5, 72-82
Henrissat,B. & Bork,P. (1996).
On the classification of modular proteins. Prot.Engng., 9, 725-726
Higgins,D.G., Thompson,J.D. & Gibson,T.J. (1996).
Using CLUSTAL for multiple sequence alignments. Methods Enzymol., 266, 383-402
Hooft,R.W.W. & Vriend,G. (1996).
Improved coordinate reconstruction from stereo diagrams.. J Mol Graph, 14, 168-172
A program has been written that reconstructs three-dimensional coordinates for a protein structure given a stereo C alpha diagram. Initial three-dimensional coordinates are determined using an algorithm similar to the one used by Rossmann in the program STEREO. Thereafter the coordinates are refined such that the stereo image based on the reconstructed three-dimensional coordinates optimally fits the scanned stereo image while normal C alpha stereochemistry is enforced.
Hooft,R.W.W., Vriend,G., Sander,C. & Abola,E.E. (1996).
Errors in protein structures. Nature , 381, 272-272
This short note in NATURE describes how more than 1,000,000 problems were detected
in the PDB using the WHAT_CHECK program. This article was submitted with the title
1000000 outliers in protein structures but NATURE changed the title without asking us.
We called all these problems deliberately outliers because in most cases we can only be
90%, 99%, 99.9%, etc., sure that a detected problem is really an error. A small but
significant fraction of the problems could represent actual features of the protein
structure. One should keep in mind that a values that deviate three sigma from the mean
should show up in about 1 per 1000 of all cases.
Chapter 23 of the WHAT IF writeup tells you which checks can be performed.
If you use our PDB structure quality reports or the WHAT_CHECK program, please refer
to this article/note.
Hooft,R.W.W., Sander,C. & Vriend,G. (1996).
Verification of protein structures: Side-chain planarity. J. Appl. Cryst., 29, 714-716
This paper describes the verification of side-chain planarity by WHAT IF and
WHAT CHECK. It also describes the construction of a representative list of PDB
files as used in the WHAT IF database.
Hooft,R.W.W., Sander,C. & Vriend,G. (1996).
The PDBFINDER database: A summary of PDB, DSSP and HSSP information with added value.. CABIOS , 12, 525-529
MOTIVATION: The Protein Data Bank currently contains more than 4700 protein coordinate sets. It is often desirable to make a selection from these files based on a criterion like R-factor, experimental method, length of the amino acid sequence, or the number of homologous sequences in SWISSPROT. Doing this using the distributed form of the Protein Data Bank can be a tedious task, because (1) this requires reading one file for every single entry, and (2) not all of the information is present in a consistent computer readable way in all of the entries. RESULTS: The PDBFINDER database provides an easy to interpret file containing summary information about all Protein Data Bank files. Summary information from the DSSP (Definition of Secondary Structure of Proteins) and HSSP (Homology derived Secondary Structure of Proteins) databases is also included. Furthermore, where essential data were missing from the Protein Data Bank file, this information has been retrieved from the original literature. AVAILABILITY: The latest version of the PDBFINDER database can be downloaded by anonymous ftp from swift.embl-heidelberg.de, directory:/pdbfinder. CONTACT: E-mail address hooft@embl-heidelberg.de.
Hooft,R.W.W., Sander,C. & Vriend,G. (1996).
Positioning hydrogen atoms by optimizing hydrogen-bond networks in protein structures. PROTEINS , 26, 363-376
This article describes the HB2 options in WHAT IF. In contrast to most other hydrogen
bond calculation programs, this method tries to optimize the whole hydrogen bonding
network of the full protein, rather than just looking around for the nearest suitable partner.
Additionally, the method looks if flipping the sidechains of Asn, Gln and His residues
might improve the hydrogen bonding network. The idea behind this is that in most Xray
projects the difference between C, N and O atoms cannot been seen. If in such cases the
local H-bond network is too complicated for the human brain to solve, the chance that the
sidechain is put into the density 'the wrong way around' is considerable.All PDB files
were looked at with this tecnique and the outcome is available on the WWW.
Huynen,M.A. & Neumann,A.U. (1996).
Rate of killing of HIV-infected T-cells and disease progression. Science, 272, 1962-1963
Huynen,M.A. (1996).
Exploring Phenotype Space Through Neutral Evolution. Journal of Molecular Evolution, 43, 165-169
Huynen,M.A., Perelson,A., Vieira,W.A. & Stadler,P.F. (1996).
Base Pairing Probabilities in a Complete HIV-1 RNA. Journal of Computational Biology, 3.2, 253-274
Huynen,M.A., Stadler,P.F. & Fontana,W. (1996).
Smoothness within ruggedness: the role of neutrality in adaptation. Proceedings of the National Academy of Sciences USA, 93, 397-401
Koonin,E.V. & Bork,P. (1996).
An ancient duplication of DNA polymerase. TIBS, 21, 128-129
Koonin,E.V., Altschul,S.F. & Bork,P. (1996).
A conserved domain in BRCA1. Nature Genet., 13, 266-268
Koonin,E.V., Mushegian,A.R. & Bork,P. (1996).
Non-orthologous gene displacement. Trends Genet., 12, 334-336
Morozov,V.M. (1996).
Structure-activity analysis of amino acid sequences using the Internet. Molecular Biology (Moscow), 2, 231-234
Musco,G., Stier,G., Joseph,C., Castiglione-Morelli,M.A., Nilges,M., Gibson,T.J. & Pastore,A. (1996).
Three-Dimensional structure and stability of the KH domain: molecular insights into the Fragile X Syndrome. Cell, 85, 237-245
Nagle,D.L., Karim,M.A., Woolf,E.A., Holmgren,L., Bork,P., Misumi,D.J., McGrail,S.H., Dussault,B.J., Perou,C.M., Boissy,R.E., Duyk,G.M., Spritz,R.A. & Moore,K.J. (1996).
Identification and mutation analysis of the complete gene for Chediak-Higashi syndrome. Nature Genet., 14, 307-311
Okumura,M., Matthew,R.J., Robb,B., Bork,P. & Thomas,M.L. (1996).
Comparison of CD45 extracellular domain sequences from divergent vertebate species suggests the conservation of 3 fibronectin type III domains. J .Immunol., 157, 1569-1575
Ponting,C. & Bork,P. (1996).
Pleckstrin's repeat performance . TIBS, 21, 245-246
Sobolev,V., Wade,R.C., Vriend,G. & Edelman,M. (1996).
Molecular docking using surface complementarity. PROTEINS, 25, 120-129
This is one of the two docking methods we are involved in. The other one is the FLEX program written in the group of T. Lengauer at the GMD in Bonn. Both with LIGIN and with FLEX, WHAT IF is used as an interface. We are only involved in discussing the scientific aspects, but not in the actual implementation. You find the interfaces in the DRUG chapter of the WHAT IF writeup. See the Additional information available on this subject.
Tatusov,R.L., Mushegian,A.R., Bork,P., Brown,N.P., Hayes,W.S., Borodovski,M., Rudd,K.E. & Koonin,E.V. (1996).
Metabolism and evolution of H.infuenza deduced from a whole genome comparison to E.coli. Curr.Biol, 6, 279-291
VanAalten,D.M., Bywater,R., Findlay,J.B., Hendlich,M., Hooft,R.W.W. & Vriend,G. (1996).
PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules. J Comput Aided Mol Des , 10, 255-262
A software package is described that operates on small molecules observed in the PDB collection of protein structures. Molecular topology files for many molecular modeling programs can be generated automatically. The three-dimensional coordinates of small molecules can be converted to molecular descriptor strings that encode them uniquely in order to enable small-molecule recognition, despite high variability in atom and molecule nomenclature. From this descriptor a plausible 3D structure can be regenerated using energy minimisation. Alternatively, an ensemble of structures can be generated using a distance-geometry-based algorithm.
Veltman,O.R., Vriend,G., Middelhoven,P.J., Van-den-Burg,B., Venema,G. & Eijsink,V.G. (1996).
Analysis of structural determinants of the stability of thermolysin-like proteases by molecular modelling and site-directed mutagenesis. Protein Eng, 9, 1181-1189
The thermolysin-like protease (TLP) produced by Bacillus stearothermophilus CU21 (TLP-ste) differs at 43 positions from the more thermally stable thermolysin (containing 316 residues in total). Of these differences, 26 were analysed by studying the effect of replacing residues in TLP-ste by the corresponding residues in thermolysin. Several stabilizing mutations were identified but, remarkably, considerable destabilizing mutational effects were also found. A Tyr-rich three residue insertion in TLP-ste (the only deletional/insertional difference between the two enzymes) appeared to make an important contribution to the stability of the enzyme. Mutations with large effects on stability were all localized in the beta-pleated N-terminal domain of TLP-ste, confirming observations that this domain has a lower intrinsic stability than the largely alpha-helical C-terminal domain. Rigidifying mutations such as Gly58-->Ala and Ala69-->Pro were among the most stabilizing ones. Apart from this observation, the analyses did not reveal general rules for stabilizing proteins. Instead, the results highlight the importance of context in evaluating the stability effects of mutations.
Walther,D., Eisenhaber,F. & Argos,P. (1996).
Principles of Helix-Helix Packings in Proteins: the Helical Lattice Superposition Model. Journal of Molecular Biology, 255, 536-553
Yajnik,V., Blaikie,P., Bork,P. & Margolis,B. (1996).
Identification of residues within the shc PTB/PI domain crucial for phosphopeptide interaction. J.Biol.Chem., 271, 1813-1816
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