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The ProFunc Function Prediction Server

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Protein Function Prediction

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1611))

Abstract

The ProFunc web server is a tool for helping identify the function of a given protein whose 3D coordinates have been experimentally determined or homology modeled. It uses a cocktail of both sequence- and structure-based methods to identify matches to other proteins that may, in turn, suggest the query protein’s most likely function. The server was originally developed to aid the worldwide structural genomics effort at the start of the millennium. It accepts a file containing the protein’s 3D coordinates in PDB format, and, when processing is complete, sends an email containing a link to the password-protected result pages. The results include an at-a-glance summary, as well as separate pages containing more detailed analyses. The server can be found at: http://www.ebi.ac.uk/thornton-srv/databases/profunc.

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References

  1. Grabowski M, Niedzialkowska E, Zimmerman MD, Minor W (2016) The impact of structural genomics: the first quindecennial. J Struct Funct Genom 17(1):1–16. doi:10.1007/s10969-016-9201-5

  2. Lee D, de Beer TA, Laskowski RA, Thornton JM, Orengo CA (2011) 1,000 structures and more from the MCSG. BMC Struct Biol 11:2. doi:10.1186/1472-6807-11-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jaroszewski L, Rychlewski L, Li Z, Li W, Godzik A (2005) FFAS03: a server for profile—profile sequence alignments. Nucleic Acids Res 33(Web Server issue):W284–W288. doi:10.1093/nar/gki418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Binkowski TA, Freeman P, Liang J (2004) pvSOAR: detecting similar surface patterns of pocket and void surfaces of amino acid residues on proteins. Nucleic Acids Res 32(Web Server issue):W555–W558. doi:10.1093/nar/gkh390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pal D, Eisenberg D (2005) Inference of protein function from protein structure. Structure 13(1):121–130. doi:10.1016/j.str.2004.10.015

    Article  CAS  PubMed  Google Scholar 

  6. Laskowski RA, Watson JD, Thornton JM (2005) ProFunc: a server for predicting protein function from 3D structure. Nucleic Acids Res 33(Web Server issue):W89–W93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Laskowski RA, Hutchinson EG, Michie AD, Wallace AC, Jones ML, Thornton JM (1997) PDBsum: a web-based database of summaries and analyses of all PDB structures. Trends Biochem Sci 22(12):488–490. doi:10.1016/S0968-0004(97)01140-7

    Article  CAS  PubMed  Google Scholar 

  8. de Beer TA, Berka K, Thornton JM, Laskowski RA (2014) PDBsum additions. Nucleic Acids Res 42(Database issue):D292–D296. doi:10.1093/nar/gkt940

    Article  PubMed  Google Scholar 

  9. Pearson WR (1990) Rapid and sensitive sequence comparison with FASTP and FASTA. Methods Enzymol 183:63–98

    Article  CAS  PubMed  Google Scholar 

  10. Berman HM, Kleywegt GJ, Nakamura H, Markley JL (2014) The Protein Data Bank archive as an open data resource. J Comput Aided Mol Des 28(10):1009–1014. doi:10.1007/s10822-014-9770-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25(17):3389–3402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. UniProt C (2015) UniProt: a hub for protein information. Nucleic Acids Res 43(Database issue):D204–D212. doi:10.1093/nar/gku989

    Google Scholar 

  13. Valdar WS, Thornton JM (2001) Conservation helps to identify biologically relevant crystal contacts. J Mol Biol 313(2):399–416. doi:10.1006/jmbi.2001.5034

    Article  CAS  PubMed  Google Scholar 

  14. Mitchell A, Chang HY, Daugherty L, Fraser M, Hunter S, Lopez R, McAnulla C, McMenamin C, Nuka G, Pesseat S, Sangrador-Vegas A, Scheremetjew M, Rato C, Yong SY, Bateman A, Punta M, Attwood TK, Sigrist CJ, Redaschi N, Rivoire C, Xenarios I, Kahn D, Guyot D, Bork P, Letunic I, Gough J, Oates M, Haft D, Huang H, Natale DA, Wu CH, Orengo C, Sillitoe I, Mi H, Thomas PD, Finn RD (2015) The InterPro protein families database: the classification resource after 15 years. Nucleic Acids Res 43(Database issue):D213–D221. doi:10.1093/nar/gku1243

    Article  PubMed  Google Scholar 

  15. Sigrist CJ, de Castro E, Cerutti L, Cuche BA, Hulo N, Bridge A, Bougueleret L, Xenarios I (2012) New and continuing developments at PROSITE. Nucleic Acids Res 41(Database issue):D344–D347. doi:10.1093/nar/gks1067

    Article  PubMed  PubMed Central  Google Scholar 

  16. Finn RD, Coggill P, Eberhardt RY, Eddy SR, Mistry J, Mitchell AL, Potter SC, Punta M, Qureshi M, Sangrador-Vegas A, Salazar GA, Tate J, Bateman A (2016) The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res 44(D1):D279–D285. doi:10.1093/nar/gkv1344

    Article  CAS  PubMed  Google Scholar 

  17. Letunic I, Doerks T, Bork P (2015) SMART: recent updates, new developments and status in 2015. Nucleic Acids Res 43(Database issue):D257–D260. doi:10.1093/nar/gku949

    Article  CAS  PubMed  Google Scholar 

  18. Attwood TK, Coletta A, Muirhead G, Pavlopoulou A, Philippou PB, Popov I, Roma-Mateo C, Theodosiou A, Mitchell AL (2012) The PRINTS database: a fine-grained protein sequence annotation and analysis resource—its status in 2012. Database (Oxford) 2012:bas019. doi:10.1093/database/bas019

    Article  Google Scholar 

  19. Gough J, Karplus K, Hughey R, Chothia C (2001) Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure. J Mol Biol 313(4):903–919. doi:10.1006/jmbi.2001.5080

    Article  CAS  PubMed  Google Scholar 

  20. Servant F, Bru C, Carrere S, Courcelle E, Gouzy J, Peyruc D, Kahn D (2002) ProDom: automated clustering of homologous domains. Brief Bioinform 3(3):246–251

    Article  CAS  PubMed  Google Scholar 

  21. Krissinel E, Henrick K (2004) Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr D Biol Crystallogr 60(Pt 12 Pt 1):2256–2268. doi:10.1107/S0907444904026460

    Article  CAS  PubMed  Google Scholar 

  22. Laskowski RA (1995) SURFNET: a program for visualizing molecular surfaces, cavities, and intermolecular interactions. J Mol Graph 13(5):323–330 . doi:10.1016/0263-7855(95)00073-9307–328

    Article  CAS  PubMed  Google Scholar 

  23. Laskowski RA, Luscombe NM, Swindells MB, Thornton JM (1996) Protein clefts in molecular recognition and function. Protein Sci 5(12):2438–2452. doi:10.1002/pro.5560051206

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Watson JD, Milner-White EJ (2002) A novel main-chain anion-binding site in proteins: the nest. A particular combination of phi,psi values in successive residues gives rise to anion-binding sites that occur commonly and are found often at functionally important regions. J Mol Biol 315(2):171–182. doi:10.1006/jmbi.2001.5227

    Article  CAS  PubMed  Google Scholar 

  25. Watson JD, Milner-White EJ (2002) The conformations of polypeptide chains where the main-chain parts of successive residues are enantiomeric. Their occurrence in cation and anion-binding regions of proteins. J Mol Biol 315(2):183–191. doi:10.1006/jmbi.2001.5228

    Article  CAS  PubMed  Google Scholar 

  26. Laskowski RA, Watson JD, Thornton JM (2005) Protein function prediction using local 3D templates. J Mol Biol 351(3):614–626

    Article  CAS  PubMed  Google Scholar 

  27. Barker JA, Thornton JM (2003) An algorithm for constraint-based structural template matching: application to 3D templates with statistical analysis. Bioinformatics 19(13):1644–1649

    Article  CAS  PubMed  Google Scholar 

  28. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The Gene ontology consortium. Nat Genet 25(1):25–29. doi:10.1038/75556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chothia C, Lesk AM (1986) The relation between the divergence of sequence and structure in proteins. EMBO J 5(4):823–826

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Todd AE, Orengo CA, Thornton JM (1999) Evolution of protein function, from a structural perspective. Curr Opin Chem Biol 3(5):548–556

    Article  CAS  PubMed  Google Scholar 

  31. Todd AE, Orengo CA, Thornton JM (2001) Evolution of function in protein superfamilies, from a structural perspective. J Mol Biol 307(4):1113–1143

    Article  CAS  PubMed  Google Scholar 

  32. Orengo CA, Jones DT, Thornton JM (1994) Protein superfamilies and domain superfolds. Nature 372(6507):631–634. doi:10.1038/372631a0

    Article  CAS  PubMed  Google Scholar 

  33. Porter CT, Bartlett GJ, Thornton JM (2004) The catalytic site atlas: a resource of catalytic sites and residues identified in enzymes using structural data. Nucleic Acids Res 32(Database issue):D129–D133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sanishvili R, Yakunin AF, Laskowski RA, Skarina T, Evdokimova E, Doherty-Kirby A, Lajoie GA, Thornton JM, Arrowsmith CH, Savchenko A, Joachimiak A, Edwards AM (2003) Integrating structure, bioinformatics, and enzymology to discover function: BioH, a new carboxylesterase from Escherichia coli. J Biol Chem 278(28):26039–26045. doi:10.1074/jbc.M303867200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kim Y, Tesar C, Mire J, Jedrzejczak R, Binkowski A, Babnigg G, Sacchettini J, Joachimiak A (2011) Structure of apo- and monometalated forms of NDM-1—a highly potent carbapenem-hydrolyzing metallo-beta-lactamase. PLoS One 6(9):e24621. doi:10.1371/journal.pone.0024621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bernstein FC, Koetzle TF, Williams GJ, Meyer EF Jr, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M (1977) The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol 112(3):535–542

    Article  CAS  PubMed  Google Scholar 

  37. Bourne PE, Berman HM, McMahon B, Watenpaugh KD, Westbrook JD, Fitzgerald PM (1997) Macromolecular crystallographic information file. Methods Enzymol 277:571–590

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

I would like to thank James Watson for writing the ProFunc tutorial on which parts of this chapter are based.

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Authors and Affiliations

  1. European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK

    Roman A. Laskowski

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  1. Roman A. Laskowski
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Correspondence to Roman A. Laskowski .

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Editors and Affiliations

  1. Department of Biological Sciences and Computer Science, Purdue University, West Lafayette, Indiana, USA

    Daisuke Kihara

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Laskowski, R.A. (2017). The ProFunc Function Prediction Server. In: Kihara, D. (eds) Protein Function Prediction. Methods in Molecular Biology, vol 1611. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7015-5_7

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  • DOI: https://doi.org/10.1007/978-1-4939-7015-5_7

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7013-1

  • Online ISBN: 978-1-4939-7015-5

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