From Protein Structure to Function with Bioinformatics.pdf

108 T. Nugent and D.T. Jonescomplexity of ab initio protein folding methods means that it is not feasible to use suchmethod for structures with more than about 150 amino acids. Several approaches mightbe used to overcome this limitation. The simplest improvement to implement for FILMwould be to construct a more restricted supersecondary structure fragment library, perhapsbased solely on membrane protein structures. This would greatly bias the fragmentsearch to conformations likely to form part of large transmembrane structures. A furtherimprovement could be achieved by using larger structure fragments than just supersecondarymotifs. Future challenges to enable ROSETTA to make predictions on largerdomains include enhanced conformational sampling strategies and more accurate treatmentof electrostatics.ReferencesAltschul SF, Koonin EV (1998) Iterated profile searches with PSI-BLAST – a tool for discoveryin protein databases. Trends Biochem Sci 23:444–447Altschul SF, Wootton JC, Gertz EM, et al. (2005) Protein database searches using compositionallyadjusted substitution matrices. FEBS J 272:5099–5100Amico M, Finelli M, Rossi I, et al. (2006) PONGO: a web server for multiple predictions of allalphatransmembrane proteins. Nucleic Acids Res 34:169–172Bagos PG, Liakopoulos TD, Spyropoulos IC, et al. (2004) A Hidden Markov Model method,capable of predicting and discriminating beta-barrel outer membrane proteins. BMCBioinformatics 5:29Bahr A, Thompson JD, Thierry JC, et al. (2001) BAliBASE (Benchmark Alignment dataBASE):enhancements for repeats, transmembrane sequences and circular permutations. Nucleic AcidsRes 29:323–326Barth P, Schonbrun J, Baker D (2007) Toward high-resolution prediction and design of transmembranehelical protein structures. Proc Natl Acad Sci USA 104:15682–15687Bendtsen JD, Nielsen H, von Heijne G, et al. (2004). Improved prediction of signal peptides:SignalP 3.0. J Mol Biol 340:783–795Bernstein FC, Koetzle TF, Williams GJB, et al. (1977) The Protein Data Bank: a computer-basedarchival file for macromolecular structures. J Mol Biol 112:535–542Boeckmann B, Bairoch A, Apweiler R, et al. (2003) The SWISS-PROT protein knowledgebaseand its supplement TrEMBL in 2003. Nucleic Acids Res 31:365–370Canutescu AA, Shelenkov AA, Dunbrack RL (2003) A graph-theory algorithm for rapid proteinside-chain prediction. Protein Sci 12:2001–2014Claros MG, von Heijne G (1994) TopPred II: an improved software for membrane protein structurepredictions. Comput Appl Biosci 10:685–686Dayhoff MO, Schwartz RM, Orcutt BC (1978) A model of evolutionary change in proteins. AtlasProtein Seq Struct 5:345–352Donizelli M, Djite MA, Le Novère N (2006) LGICdb: a manually curated sequence database afterthe genomes. Nucleic Acids Res 34:267–269Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput.Nucleic Acids Res 32:1792–1797Emanuelsson O, Brunak S, von Heijne G, et al. (2007) Locating proteins in the cell using TargetP,SignalP and related tools. Nat Protoc 2:953–971Engelman DM, Steitz TA, Goldman A (1986) Identifying nonpolar transbilayer helices in aminoacid sequences of membrane proteins. Annu Rev Biophys Biophys Chem 15:321–353Forrest LR, Tang CL, Honig B (2006) On the accuracy of homology modeling and sequence alignmentmethods applied to membrane proteins. Biophys J 91:508–517