From Protein Structure to Function with Bioinformatics.pdf

82 A. FiserImproved and new methods to refine comparative models by adding accurateloops and side chains, refining internal packing of secondary structural elements,setting up scoring functions that can measure model quality, optimally combiningfragments from known folds and detecting errors in the 3D models are criticalissues. Even a small improvement in these techniques will have a large impactbecause most of the protein structural relationships are too remote to utilize themin comparative modelling. On the other hand, while improvements in these topicsmay not have a significant impact on the overall accuracy of already existing proteinmodels, their importance in achieving functionally more reliable 3D models i.e.models that can confidently be used for functional annotation, can not be emphasizedenough.The above advances in comparative protein structure modelling techniques arenecessary prerequisites to develop new “structural proteomics” modelling methodswith the aim of combining the basic building blocks of fold models into physiologicallymore relevant quaternary structures and assemblies. This will create possibilitiesfor modelling interactions among the many known protein structures.Acknowledgments This review is partially based on our previous publication (Fiser 2004).ReferencesAbagyan R, Totrov M (1994) Biased probability Monte Carlo conformational searches and electrostaticcalculations for peptides and proteins. J Mol Biol 235:983–1002Alber F, Dokudovskaya S, Veenhoff LM, et al. (2007a) Determining the architectures of macromolecularassemblies. Nature 450:683–694Alber F, Dokudovskaya S, Veenhoff LM, et al. (2007b) The molecular architecture of the nuclearpore complex. Nature 450:695–701Alber F, Forster F, Korkin D, et al. (2008) Integrating diverse data for structure determination ofmacromolecular assemblies. Annu Rev Biochem 77:443–477Al Lazikani B, Sheinerman FB, Honig B (2001) Combining multiple structure and sequencealignments to improve sequence detection and alignment: application to the SH2 domains ofJanus kinases. Proc Natl Acad Sci USA 98:14796Altschul SF, Madden TL, Schaffer AA, et al. (1997) Gapped BLAST and PSI-BLAST: a newgeneration of protein database search programs. Nucleic Acids Res 25:3389–3402Andreeva A, Howorth D, Chandonia JM, et al. (2008) Data growth and its impact on the SCOPdatabase: new developments. Nucleic Acids Res 36:D419–425Apostolico A, Giancarlo R (1998) Sequence alignment in molecular biology. J Comput Biol5:173–196Apweiler R, Bairoch A, Wu CH (2004) Protein sequence databases. Curr Opin Chem Biol8:76–80Aszodi A, Taylor WR (1994) Secondary structure formation in model polypeptide chains. ProteinEng 7:633–644Aszodi A, Taylor WR (1996) Homology modelling by distance geometry. Fold Des 1:325–334Baker D, Sali A (2001) Protein structure prediction and structural genomics. Science294:93–96Barrientos LG, Campos-Olivas R, Louis JM, et al. (2001) 1H, 13C, 15N resonance assignmentsand fold verification of a circular permuted variant of the potent HIV-inactivating proteincyanovirin-N. J Biomol NMR 19:289–290