Structural bioinformatics: Deriving biological insights from protein structures

Article

Abstract

Structural bioinformatics can be described as an approach that will help decipher biological insights from protein structures. As an important component of structural biology, this area promises to provide a high resolution understanding of biology by assisting comprehension and interpretation of a large amount of structural data. Biological function of protein molecules can be inferred from their three-dimensional structures by comparing structures, classifying them and transferring function from a related protein or family. It is well known now that the structure space of protein molecules is more conserved than the sequence space, making it important to seek functional associations at the structural level. An added advantage of structural bioinformatics over simpler sequence-based methods is that the former also provides ultimate insights into the mechanisms by which various biological events take place. A bird’s eye-view of the different aspects of structural bioinformatics is given here along with various recent advances in the area including how knowledge obtained from structural bioinformatics can be applied in drug discovery.

Key words

protein structures structural genomics structure-function relationship structural analysis biological data mining 

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References

  1. [1]
    Aloy, P., Russell, R.B. 2006. Structural systems biology: Modelling protein interactions. Nat Rev Mol Cell Biol 7, 188–197.PubMedCrossRefGoogle Scholar
  2. [2]
    An, J., Totrov, M., Abagyan, R. 2005. Pocketome via comprehensive identification and classification of ligand binding envelopes. Mol Cell Proteomics 4, 752–761.PubMedCrossRefGoogle Scholar
  3. [3]
    Ananthalakshmi, P., Samayamohan, K., Chokalingam, C., Mayilarasi, C., Sekar, K. 2005. Psst-2.0: Protein data bank sequence search tool. Applied Bioinformatics 4, 141–145.PubMedCrossRefGoogle Scholar
  4. [4]
    Andreeva, A., Howorth, D., Chandonia, J.M., Brenner, S.E., Hubbard, T.J.P., Chothia, C., Murzin, A.G. 2008. Data growth and its impact on the scop database: New developments. Nucleic Acids Research 36, D419–D425.PubMedCrossRefGoogle Scholar
  5. [5]
    Baldus, M. 2006. Molecular interactions investigated by multi-dimensional solid-state nmr. Curr Opin Struct Biol 16, 618–623.PubMedCrossRefGoogle Scholar
  6. [6]
    Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E. 2000. The protein data bank. Nucleic Acids Research 28, 235–242.PubMedCrossRefGoogle Scholar
  7. [7]
    Bernstein, B.E., Williams, D.M., Bressi, J.C., Kuhn, P., Gelb, M.H., Blackburn, G.M., Hol, W.G. 1998. A bisubstrate analog induces unexpected conformational changes in phosphoglycerate kinase from trypanosoma brucei. J Mol Biol 279, 1137–1148.PubMedCrossRefGoogle Scholar
  8. [8]
    Bharath, M.M.S., Chandra, N.R., Rao, M.R.S. 2003. Molecular modeling of the chromatosome particle. Nucleic Acids Research 31, 4264–4274.PubMedCrossRefGoogle Scholar
  9. [9]
    Bhat, T.N., Saikrishnan, V., Vijayan, M. 1979. An analysis of side chain conformation in proteins. International Journal of Peptide and Protein Research 13, 170–184.PubMedCrossRefGoogle Scholar
  10. [10]
    Bhattacharya, S., Bhattacharyya, C., Chandra, N.R. 2006. Projections for fast protein structure retrieval. BMC Bioinformatics 7,Suppl 5, S5.PubMedCrossRefGoogle Scholar
  11. [11]
    Bhinge, A., Chakrabarti, P., Uthanumallian, K., Bajaj, K., Chakraborty, K.R. 2004. Accurate detection of protein: Ligand binding sites using molecular dynamics simulations. Structure 12, 1989–1999.PubMedCrossRefGoogle Scholar
  12. [12]
    Bohm, H.-J. 1994. On the use of ludi to search the fine chemicals directory for ligands of proteins of known three-dimensional structure. Journal of Computer-Aided Molecular Design 8, 623–632.PubMedCrossRefGoogle Scholar
  13. [13]
    Bourne, P.E., Weissig, H. 2008. Structural Bioinformatics. Wiley InterScience, New York.Google Scholar
  14. [14]
    Bowie, J.U., Luthy, R., Eisenberg, D. 1991. A method to identify protein sequences that fold into a known three-dimensional structure. Science 253, 164–170.PubMedCrossRefGoogle Scholar
  15. [15]
    Brady, G.P., Stouten, P.F. 2000. Fast prediction and visualization of protein binding pockets with pass. J Comput Aided Mol Des 14, 383–401.PubMedCrossRefGoogle Scholar
  16. [16]
    Brylinski, M., Kochanczyk, M., Broniatowska, E., Roterman, I. 2007. Localization of ligand binding site in proteins identified in silico. J Mol Model 13, 665–675.PubMedCrossRefGoogle Scholar
  17. [17]
    Burley, S.K. 2000. An overview of structural genomics. Nature Structure and Molecular Biology 7, 932–934.CrossRefGoogle Scholar
  18. [18]
    Cai, W., Shao, X., Maigret, B. 2002. Protein-ligand recognition using spherical harmonic molecular surfaces: Towards a fast and efficient filter for large virtual throughput screening. J Mol Graph Model 20, 313–328.PubMedCrossRefGoogle Scholar
  19. [19]
    Card, G.L., Peterson, N.A., Smith, C.A., Rupp, B., Schick, B.M., Baker, E.N. 2005. The crystal structure of rv1347c, a putative antibiotic resistance protein from mycobacterium tuberculosis, reveals a gcn5-related fold and suggests an alternative function in siderophore biosynthesis. J Biol Chem 280, 13978–13986.PubMedCrossRefGoogle Scholar
  20. [20]
    Chakrabarti, S., Lanczycki, C.J. 2007. Analysis and prediction of functionally important sites in proteins. Protein Sci 16, 4–13.PubMedCrossRefGoogle Scholar
  21. [21]
    Chandra, N., Kumar, N., Jeyakani, J., Singh, D., Gowda, S., Prathima, M. 2006. Lectindb: A plant lectin database. Glycobiology 16, 938–946.PubMedCrossRefGoogle Scholar
  22. [22]
    Chandra, N., Muirhead, H., Holbrook, J., Bernstein, B., Hol, W., Sessions, R. 1998. A general method of domain closure is applied to phosphoglycerate kinase and the result compared with the crystal structure of a closed conformation of the enzyme. Proteins 30, 372–380.PubMedCrossRefGoogle Scholar
  23. [23]
    Chen, R. 2001. Enzyme engineering: Rational redesign versus directed evolution. Trends Biotechnol 19, 13–14.PubMedCrossRefGoogle Scholar
  24. [24]
    Cheng, H., Kim, B.H., Grishin, N.V. 2008. Malisam: A database of structurally analogous motifs in proteins. Nucleic Acids Res 36(Database issue), 211–217.Google Scholar
  25. [25]
    Chiu, W., Baker, M.L., Jiang, W., Dougherty, M., Schmid, M.F. 2005. Electron cryomicroscopy of biological machines at subnanometer resolution. Structure 13, 363–372.PubMedCrossRefGoogle Scholar
  26. [26]
    Coleman, R.G., Salzberg, A.C., Cheng, A.C. 2006. Structure based identification of small molecule binding sites using free energy model. J Chem Inf Model 46, 2631–2637.PubMedCrossRefGoogle Scholar
  27. [27]
    Congreve, M., Murray, C.W., Blundell, T.L. 2005. Structural biology and drug discovery. Drug Discovery Today 10, 895–907.PubMedCrossRefGoogle Scholar
  28. [28]
    Cozzetto, D., Kryshtafovych, A., Fidelis, K., Moult, J., Rost, B., Tramontano, A. 2009. Evaluation of template-based models in casp8 with standard measures. Proteins 77Suppl 9, 18–28.PubMedGoogle Scholar
  29. [29]
    Dandekar, T., Snel, B., Huynen, M., Bork, P. 1998. Conservation of gene order: A fingerprint of proteins that physically interact. Trends Biochem Sci 23, 324–328.PubMedCrossRefGoogle Scholar
  30. [30]
    Dessailly, B.H., Lensink, M.F., Orengo, C.A., Wodak, S.J. 2008. Ligasite — a database of biologically relevant binding sites in proteins with known apo-structures. Nucleic Acids Res 36(Database issue), 667–673.Google Scholar
  31. [31]
    Dimitropoulos, D., Ionides, J., Henrick, K. 2006. Using msdchem to search the pdb ligand dictionary. Curr Protoc Bioinformatics, Chapter 14.Google Scholar
  32. [32]
    Dodson, G., Verma, C.S. 2006. Protein flexibility: Its role in structure and mechanism revealed by molecular simulations. Cell Mol Life Sci 63, 207–219.PubMedCrossRefGoogle Scholar
  33. [33]
    Dunbrack, R.L., Karplus, M. 1994. Conformational analysis of the backbone-dependent rotamer preferences of protein sidechains. Nat Struct Biol 1, 334–340.PubMedCrossRefGoogle Scholar
  34. [34]
    Enright, A.J., Ouzounis, C.A. 2001. Functional associations of proteins in entire genomes by means of exhaustive detection of gene fusions. Genome Biol 2.Google Scholar
  35. [35]
    Ewing, T.J.A., Kuntz, I.D. 1998. Critical evaluation of search algorithms for automated molecular docking and database screening. Journal of Computational Chemistry 18, 1175–1189.CrossRefGoogle Scholar
  36. [36]
    Ferrè F., Ausiello, G., Zanzoni, A., Helmer-Citterich, M. 2004. Surface: A database of protein surface regions for functional annotation. Nucleic Acids Res 32(Database issue), 240–244.CrossRefGoogle Scholar
  37. [37]
    Flieschmann, R.D., Adams, M.D., White, O. Clayton, R.A., Kirkness, E.F., Kerlavage, A.R., Bult, C.J., Tomb, J.F., Dougherty, B.A., Merrick, J.M. 1995. Whole-genome random sequencing and assembly of haemophilus influenzaerd. Science 269, 496–512.CrossRefGoogle Scholar
  38. [38]
    Flores, S., Echols, N., Milburn, D., Hespenheide, B., Keating, K., Lu, J., Wells, S., Yu, E.Z., Thorpe, M., Gerstein, M., 2006. The database of macromolecular motions: New features added at the decade mark. Nucleic Acids Res 34(Database issue), D296–D301.PubMedCrossRefGoogle Scholar
  39. [39]
    Forster, A.C., Church, G.M. 2006. Towards synthesis of a minimal cell. Mol Syst Biol 2, 45.PubMedCrossRefGoogle Scholar
  40. [40]
    Frey, T.G., Perkins, G.A., Ellisman, M.H. 2006. Electron tomography of membrane-bound cellular organelles. Annu Rev Biophys Biomol Struct 35, 199–224.PubMedCrossRefGoogle Scholar
  41. [41]
    Gabb, H.A., Jackson, R.M., Sternberg, M.J. 1997. Modelling protein docking using shape complementarity, electrostatics and biochemical information. J Mol Biol 272, 106–120.PubMedCrossRefGoogle Scholar
  42. [42]
    Ghosh, A., Vishveshwara, S. 2007. A study of communication pathways in methionyl-trna synthetase by molecular dynamics simulations and structure network analysis. Proc Natl Acad Sci USA 104, 15711–15716.PubMedCrossRefGoogle Scholar
  43. [43]
    Glaser, F., Morris, R.J., Najmanovich, R.J., Laskowski, R.A., Thornton, J.M. 2006. A method for localizing ligand binding pockets in protein structures. Proteins 62, 479–488.PubMedCrossRefGoogle Scholar
  44. [44]
    Gold, N.D., Jackson, R.M. 2006. Sitesbase: A database for structur-based protein-ligand binding site comparisons. Nucleic Acids Research 34, D231–D234.PubMedCrossRefGoogle Scholar
  45. [45]
    Goodford, P.J., 1985. A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. J Med Chem 28, 849–857.PubMedCrossRefGoogle Scholar
  46. [46]
    Gopalakrishnan, V., Livingston, G., Hennessy, D., Buchanan, B., Rosenberg, J.M. 2004. Machinelearning techniques for macromolecular crystallization data. Acta Crystallogr D Biol Crystallogr 60(Pt 10), 1705–1716.PubMedCrossRefGoogle Scholar
  47. [47]
    Goulding, C.W., Perry, L.J., Anderson, D., Sawaya, M.R., Cascio, D., Apostol, M.I., Chan, S., Parseghian, A., Wang, S.S., Wu, Y., Cassano, V., Gill, H.S., Eisenberg, D. 2003. Structural genomics of mycobacterium tuberculosis: A preliminary report of progress at ucla. Biophys Chem 105, 361–370.PubMedCrossRefGoogle Scholar
  48. [48]
    Gowri, V.S., Pandit, S.B., Karthik, P.S., Srinivasan, N., Balaji, S. 2003. Integration of related sequences with protein three-dimensional structural families in an updated version of pali database. Nucleic Acids Res 31, 486–488.PubMedCrossRefGoogle Scholar
  49. [49]
    Guharoy, M., Chakrabarti, P. 2005. Conservation and relative importance of residues across protein-protein interfaces. Proc Natl Acad Sci USA 102, 15447–15452.PubMedCrossRefGoogle Scholar
  50. [50]
    Hendlich, M., Rippmann, F., Barnickel, G. 1997. Ligsite: Automatic and efficient detection of potential small molecule-binding sites in proteins. J Mol Graph Model 15, 359–363.PubMedCrossRefGoogle Scholar
  51. [51]
    Hennessy, D., Buchanan, B., Subramanian, D., Wilkosz, P.A., Rosenberg, J.M. 2000. Statistical methods for the objective design of screening procedures for macromolecular crystallization. Acta Crystallogr D Biol Crystallogr 56(Pt 7), 817–827.PubMedCrossRefGoogle Scholar
  52. [52]
    Hillisch, A., Pineda, L.F., Hilgenfeld, R. 2004. Utility of homology models in the drug discovery process. Drug Discov Today 9, 659–669.PubMedCrossRefGoogle Scholar
  53. [53]
    Holm, L., Sander, C. 1993. Protein structure comparison by alignment of distance matrices. J Mol Biol 233, 123–138.PubMedCrossRefGoogle Scholar
  54. [54]
    Holm, L., Sander, C., 1996. Mapping the protein universe. Science 273, 595–603.PubMedCrossRefGoogle Scholar
  55. [55]
    Holm, L., Sander, C. 1998. Touring protein fold space with dali/fssp. Nucleic Acids Res 26, 316–319.PubMedCrossRefGoogle Scholar
  56. [56]
    Hong, M. 2006. Oligomeric structure, dynamics, and orientation of membrane proteins from solid-state nmr. Structure 14, 1731–1740.PubMedCrossRefGoogle Scholar
  57. [57]
    Huang, B., Schroeder, M., 2006. Ligsitecsc: Predicting ligand binding sites using the connolly surface and degree of conservation. BMC Struct Biol 6, 19.PubMedCrossRefGoogle Scholar
  58. [58]
    Huang, T.W., Tien, A.C., Huang, W.S., Lee, Y.C., Peng, C.L., Tseng, H.H., Kao, C.Y., Huang, C.Y. 2004. Point: A database for the prediction of proteinprotein interactions based on the orthologous interactome. Bioinformatics 20, 3273–3276.PubMedCrossRefGoogle Scholar
  59. [59]
    Ilari, A., Savino, C. 2008. Protein structure determination by x-ray crystallography. Methods Mol Biol 452, 63–87.PubMedCrossRefGoogle Scholar
  60. [60]
    Jackson, T. 1991. Structure and function of g protein coupled receptors. Pharmacol Ther 50, 425–442.PubMedCrossRefGoogle Scholar
  61. [61]
    Jiang, W., Ludtke, S.J. 2005. Electron cryomicroscopy of single particles at subnanometer resolution. Curr Opin Struct Biol 15, 571–577.PubMedCrossRefGoogle Scholar
  62. [62]
    Jones, C. 2005. Vaccines based on the cell surface carbohydrates of pathogenic bacteria. An Acad Bras Cienc 77, 293–324.PubMedGoogle Scholar
  63. [63]
    Jones, D.T., Taylor, W.R., Thornton, J.M. 1992. A new approach to protein fold recognition. Nature 358, 86–89.PubMedCrossRefGoogle Scholar
  64. [64]
    Jones, S., Thornton, J.M. 1997a. Prediction of protein-protein interaction sites using patch analysis. J Mol Biol 272, 133–143.PubMedCrossRefGoogle Scholar
  65. [65]
    Kalidas, Y., Chandra, N. 2008a. Pocketdepth: A new depth based algorithm for identification of ligand binding sites in proteins. Journal of structural biology 161, 31–42.PubMedCrossRefGoogle Scholar
  66. [66]
    Kelley, L.A., Maccallum, R.M., Sternberg, M.J. 2000. Enhanced genome annotation using structural pro-files in the program 3d-pssm. J Mol Biol 299, 499–520.PubMedCrossRefGoogle Scholar
  67. [67]
    Kendrew, J.C., Bodo, G., Dintzis, H.M., Parrish, R.G., Wyckoff, H., Phillips, D.C. 1958. A three-dimensional model of the myoglobin molecule obtained by x-ray analysis. Nature 181, 662–666.PubMedCrossRefGoogle Scholar
  68. [68]
    Kern, D., Volkman, B.F., Luginbühl, P., Nohaile, M.J., Kustu, S., Wemmer, D.E. 1999. Structure of a transiently phosphorylated switch in bacterial signal transduction. Nature 402, 894–898.PubMedCrossRefGoogle Scholar
  69. [69]
    Kleywegt, G.J. 1999. Recognition of spatial mofits in protein structures. Journal of Molecular Biology 285, 1887–1897.PubMedCrossRefGoogle Scholar
  70. [70]
    Kleywegt, G.J., Jones, T.A. 1994. Detection, delineation, measurement and display of cavities in macromolecular structures. Acta Crystallogr D Biol Crystallogr 50, 178–185.PubMedCrossRefGoogle Scholar
  71. [71]
    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, 2256–2268.PubMedCrossRefGoogle Scholar
  72. [72]
    Kuhn, D., Weskamp, N., Hüllermeier, E., Klebe, G. 2007. Functional classification of protein kinase binding sites using cavbase. ChemMedChem 2, 1432–1447.PubMedCrossRefGoogle Scholar
  73. [73]
    Kyrpides, N.C. 1999. Genomes online database (gold 1.0): A monitor of complete and ongoing genome projects world-wide. Bioinformatics 15, 773–774.PubMedCrossRefGoogle Scholar
  74. [74]
    Landon, M.R., Lancia Jr., D.R., Yu, J., Thiel, S.C., Vajda, S. 2007. Identification of hot spots within druggable binding regions by compuatational solvent mapping of proteins. J Med Chem 50, 1231–1240.PubMedCrossRefGoogle Scholar
  75. [75]
    Laskowski, R.A., Macarthur, M.W., Moss, D.S., Thornton, J.M. 1993. Procheck: A program to check the stereochemical quality of protein structures. Journal of Applied Crystallography 26, 283–291.CrossRefGoogle Scholar
  76. [76]
    Laskowski, R.A., Watson, J.D., Thornton, J.M. 2005. Profunc: A server for predicting protein function from 3d structure. Nucleic Acids Res 33, 89–93.CrossRefGoogle Scholar
  77. [77]
    Laurie, A.T., Jackson, R.M. 2005. Q-sitefinder: An energy-based method for the prediction of proteinligand binding sites. Bioinformatics 21, 1908–1916.PubMedCrossRefGoogle Scholar
  78. [78]
    Lee, D., Redfern, O., Christine Orengo, C.A. 2007. Predicting protein function from sequence and structure. Nature Reviews Molecular Cell Biology 8, 995–1005.PubMedCrossRefGoogle Scholar
  79. [79]
    Lesley, S.A., Kuhn, P., Godzik, A., Deacon, A.M., Mathews, I., Kreusch, A., Spraggon, G., Klock, H.E., Mcmullan, D., Shin, T., Vincent, J., Robb, A., Brinen, L.S., Miller, M.D., Mcphillips, T.M., Miller, M.A., Scheibe, D., Canaves, J.M., Guda, C., Jaroszewski, L., Selby, T.L., Elsliger, M.A., Wooley, J., Taylor, S.S., Hodgson, K.O., Wilson, I.A., Schultz, P.G., Stevens, R.C. 2002. Structural genomics of the thermotoga maritima proteome implemented in a high-throughput structure determination pipeline. Proc Natl Acad Sci USA 99, 11664–11669.PubMedCrossRefGoogle Scholar
  80. [80]
    Levitt, D.G., Banaszak, L.J. 1992. Pocket: A computer graphics method for identifying and displaying protein cavities and their surrounding amino acids. J Mol Graph 10, 229–234.PubMedCrossRefGoogle Scholar
  81. [81]
    Liang, J., Edelsbrunner, H., Woodward, C. 1998. Anatomy of protein pockets and cavities: Measurement of binding site geometry and implications for ligand design. Protein Sci 7, 1884–1897.PubMedCrossRefGoogle Scholar
  82. [82]
    Linnainmaa, S., Harwood, D.A., Davis, L.S. 1988. Pose determination of a three-dimensional object using triangle pairs. IEEE Transactions on Pattern Analysis and Machine Intelligence 10, 634–647.CrossRefGoogle Scholar
  83. [83]
    Liolios, K., Mavromatis, K., Tavernarakis, N., Kyrpides, N.C. 2008. The genomes on line database (gold) in 2007: Status of genomic and metagenomic projects and their associated metadata. Nucleic Acids Res 36, D475–D479.PubMedCrossRefGoogle Scholar
  84. [84]
    Lo, W.C., Huang, P.J., Chang, C.H., Lyu, P.C. 2007. Protein structural similarity search by ramachandran codes. BMC Bioinformatics 8, 307.PubMedCrossRefGoogle Scholar
  85. [85]
    Lucic, V., Förster, F., Baumeister, W. 2005. Structural studies by electron tomography: From cells to molecules. Annu Rev Biochem 74, 833–865.PubMedCrossRefGoogle Scholar
  86. [86]
    Marsden, R.L., Lewis, T.A., Orengo, C.A. 2007. Towards a comprehensive structural coverage of completed genomes: A structural genomics viewpoint. BMC Bioinformatics 8, 86.PubMedCrossRefGoogle Scholar
  87. [87]
    Mcdermott, A.E. 2004. Structural and dynamic studies of proteins by solid-state nmr spectroscopy: Rapid movement forward. Curr Opin Struct Biol 14, 554–561.PubMedCrossRefGoogle Scholar
  88. [88]
    Mcguffin, L.J., Bryson, K., Jones, D.T. 2000. The psipred protein structure prediction server. Bioinformatics 16, 404–405.PubMedCrossRefGoogle Scholar
  89. [89]
    Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., Olson, A.J. 1999. Automated docking using a lamarckian genetic algorithm and an empirical binding free energy function. Journal of Computational Chemistry 19, 1639–1662.CrossRefGoogle Scholar
  90. [90]
    Moult, J. 2005. A decade of casp: Progress, bottlenecks and prognosis in protein structure prediction. Curr Opin Struct Biol 15, 285–289.PubMedCrossRefGoogle Scholar
  91. [91]
    Moult, J., Fidelis, K., Kryshtafovych, A., Rost, B., Hubbard, T., Tramontano, A. 2007. Critical assessment of methods of protein structure predictionround vii. Proteins 69Suppl 8, 3–9.PubMedCrossRefGoogle Scholar
  92. [92]
    Moult, J., Pedersen, J.T., Judson, R., Fidelis, K. 1995. A large-scale experiment to assess protein structure prediction methods. Proteins 23.Google Scholar
  93. [93]
    Muegge, I., Martin, Y.C. 1999. A general and fast scoring function for protein-ligand interactions: A simplified potential approach. Journal of Medicinal Chemistry 42, 791–804.PubMedCrossRefGoogle Scholar
  94. [94]
    Murzin, A.G., Brenner, S.E., Hubbard, T., Chothia, C. 1995. Scop: A structural classification of proteins database for the investigation of sequences and structures. Journal of Molecular Biology 247, 536–540.PubMedGoogle Scholar
  95. [95]
    Nair, A., Bonin, I., Tossi, A., Wels, W., Miertus, S. 2002. Computational studies of the resistance patterns of mutant hiv-1 aspartic proteases towards abt-538 (ritonavir) and design of new derivatives. J Mol Graph Model 21, 171–179.PubMedCrossRefGoogle Scholar
  96. [96]
    Needleman, S.B., Wunsch, C.D. 1970. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol 48, 443–453.PubMedCrossRefGoogle Scholar
  97. [97]
    O’conner, S.E., Imperiali, B. 1998. A molecular basis for glycosylation-induced conformational switching. Chem Biol 5, 427–437.PubMedCrossRefGoogle Scholar
  98. [98]
    O’donoghue, S.I., Goodsell, D.S., Frangakis, A.S., Jossinet, F., Laskowski, R.A., Nilges, M., Saibil, H.R., Schafferhans, A., Wade, R.C., Westhof, E., Olson, A.J. 2010. Visualization of macromolecular structures. Nat Methods 7(3 Suppl), S42–S55.PubMedCrossRefGoogle Scholar
  99. [99]
    Ondetti, M., Rubin, B., Cushman, D. 1977. Design of specific inhibitors of angiotensin-converting enzyme: New class of orally active antihypertensive agents. Science 196, 441–444.PubMedCrossRefGoogle Scholar
  100. [100]
    Orengo, C.A., Michie, A.D., Jones, S., Jones, D.T., Swindells, M.B., Thornton, J.M. 1997. Cath-a hierarchic classification of protein domain structures. Structure 5, 1093–1108.PubMedCrossRefGoogle Scholar
  101. [101]
    Peitsch, M.C. 1997. Large scale protein modelling and model repository. Proc Int Conf Intell Syst Mol Biol 5, 234–236.PubMedGoogle Scholar
  102. [102]
    Peng, H., Huang, N., Qi, J., Xie, P., Xu, C., Wang, J., Yang, C. 2003. Identification of novel inhibitors of bcr-abl tyrosine kinase via virtual screening. Bioorganic and Medicinal Chemistry Letters 13, 3693–3699.PubMedCrossRefGoogle Scholar
  103. [103]
    Peters, K.P., Fauck, J., Frömmel, C. 1996. The automatic search for ligand binding sites in proteins of known three-dimensional structure using only geometric criteria. Journal of Molecular Biology 256, 210–213.CrossRefGoogle Scholar
  104. [104]
    Pieper, U., Eswar, N., Braberg, H., Madhusudhan, M.S., Davis, F.P., Stuart, A.C., Mirkovic, N., Rossi, A., Marti-Renom, M.A., Fiser, A., Webb, B., Greenblatt, D., Huang, C.C., Ferrin, T.E., Sali, A. 2004. Modbase, a database of annotated comparative protein structure models, and associated resources. Nucleic Acids Res 32, 217–222.CrossRefGoogle Scholar
  105. [105]
    Pillardy, J., Czaplewski, C., Liwo, A., Lee, J., Ripoll, D.R., Kázmierkiewicz, R., Oldziej, S., Wedemeyer, W.J., Gibson, K.D., Arnautova, Y.A., Saunders, J., Ye, Y.J., Scheraga, H.A. 2001. RRecent improvements in prediction of protein structure by global optimization of a potential energy function. Proc Natl Acad Sci USA 98, 2329–2333.PubMedCrossRefGoogle Scholar
  106. [106]
    Pugalenthi, G., Suganthan, P.N., Sowdhamini, R., Chakrabarti, S. 2007. Smotif: A server for structural motifs in proteins. Bioinformatics 23, 637–638.PubMedCrossRefGoogle Scholar
  107. [107]
    Pugalenthi, G., Suganthan, P.N., Sowdhamini, R., Chakrabarti, S. 2008. Megamotifbase: A database of structural motifs in protein families and superfamilies. Nucleic Acids Res 36, 218–221.CrossRefGoogle Scholar
  108. [108]
    Qi, G., Hayward, S. 2009. Database of ligand-induced domain movements in enzymes. BMC Struct Biol 9, 13.PubMedCrossRefGoogle Scholar
  109. [109]
    Ramachandran, G.N., Ramakrishnan, C., Sasisekharan, V. 1963. Stereochemistry of polypeptide chain configurations. J Mol Biol 7, 95–99.PubMedCrossRefGoogle Scholar
  110. [110]
    Raman, K., Yeturu, K., Chandra, N. 2008. Targettb: A target identification pipeline for mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis. BMC Syst Biol 2, 109.PubMedGoogle Scholar
  111. [111]
    Rarey, M., Kramer, B., Lengauer, T., Klebe, G. 1996. A fast flexible docking method using an incremental construction algorithm. J Mol Biol 261, 470–489.PubMedCrossRefGoogle Scholar
  112. [112]
    Renault, L., Chou, H.-T., Chiu, P.-L., Hill, R.M., Zeng, X., Gipson, B., Zhang, Z.Y., Cheng, A., Unger, V., Stahlberg, H. 2006. Milestones in electron crystallography. J Comput Aided Mol Des 20, 519–527.PubMedCrossRefGoogle Scholar
  113. [113]
    Richardson, D.C., Richardson, J.S. 1992. The kinemage: A tool for scientific communication. Protein Sci 1, 3–9.PubMedCrossRefGoogle Scholar
  114. [114]
    Rost, B., Schneider, R., Sander, C. 1997. Protein fold recognition by prediction-based threading. J Mol Biol 270, 471–480.PubMedCrossRefGoogle Scholar
  115. [115]
    Russell, R.B., Saqi, M.A., Sayle, R.A., Bates, P.A., Sternberg, M.J. 1997. Recognition of analogous and homologous protein folds: Analysis of sequence and structure conservation. J Mol Biol 269, 423–439.PubMedCrossRefGoogle Scholar
  116. [116]
    Sacchettini, J.C., Baum, L.G., Brewer, C.F. 2001. Multivalent protein-carbohydrate interactions. A new paradigm for supermolecular assembly and signal transduction. Biochemistry 40, 3009–3015.PubMedCrossRefGoogle Scholar
  117. [117]
    Sánchez, R., Sali, A. 1997. Advances in comparative protein-structure modelling. Curr Opin Struct Biol 7, 206–214.PubMedCrossRefGoogle Scholar
  118. [118]
    Sayers, E. 2005. Pubchem: An entrez database of small molecules. NLM Technical Bulletin 342, e2.Google Scholar
  119. [119]
    Scapin, G. 2006. Structural biology and drug discovery. Curr Pharm Des 12, 2087–2097.PubMedCrossRefGoogle Scholar
  120. [120]
    Schlessinger, A., Rost, B. 2005. Protein flexibility and rigidity predicted from sequence. Proteins 61, 115–126.PubMedCrossRefGoogle Scholar
  121. [121]
    Schultz-Heienbrok, R., Maier, T., Sträter, N. 2005. A large hinge bending domain rotation is necessary for the catalytic function of escherichia coli 5′-nucleotidase. Biochemistry 44, 2244–2252.PubMedCrossRefGoogle Scholar
  122. [122]
    Seiler, K.P., George, G.A., Happ, M.P., Bodycombe, N.E., Carrinski, H.A., Norton, S., Brudz, S., Sullivan, J.P., Muhlich, J., Serrano, M., Ferraiolo, P., Tolliday, N.J., Schreiber, S.L., Clemons, P.A. 2008. Chembank: A small-molecule screening and cheminformatics resource database. Nucleic Acids Res 36, 351–359.CrossRefGoogle Scholar
  123. [123]
    Shin, J.-M., Cho, D.-H. 2005. Pdb-ligand: A ligand database based on pdb for the automated and customized classification of ligand-binding structures. Nucleic Acids Research 33, D238–D241.PubMedCrossRefGoogle Scholar
  124. [124]
    Shindyalov, I.N., Bourne, P.E. 1998. Protein structure alignment by incremental combinatorial extension (ce) of the optimal path. Protein Eng 11, 739–747.PubMedCrossRefGoogle Scholar
  125. [125]
    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.PubMedCrossRefGoogle Scholar
  126. [126]
    Sobolev, V., Sorokine, A., Prilusky, J., Abola, E.E., Edelman, M. 1999. Automated analysis of interatomic contacts in proteins. Bioinformatics 15, 327–332.PubMedCrossRefGoogle Scholar
  127. [127]
    Soga, S., Shirai, H., Kobori, M., Hirayama, N. 2007. Use of amino acid composition to predict ligandbinding sites. J Chem Inf Model 47, 400–406.PubMedCrossRefGoogle Scholar
  128. [128]
    Sowdhamini, R., Burke, D.F., Huang, J.F., Mizuguchi, K., Nagarajaram, H.A., Srinivasan, N., Steward, R.E., Blundell, T.L. 1998. Campass: A database of structurally aligned protein superfamilies. Structure 6, 1087–1094.PubMedCrossRefGoogle Scholar
  129. [129]
    Stark, A., Russell, R.B. 2003. Annotation in three dimensions. Pints: Patterns in non-homologous tertiary structures. Nucleic Acids Research 31, 3341–3344.Google Scholar
  130. [130]
    Sun, S. 1993. Reduced representation model of protein structure prediction: Statistical potential and genetic algorithms. Protein Sci 2, 762–785.PubMedCrossRefGoogle Scholar
  131. [131]
    Szustakowski, J.D., Weng, Z. 2000. Protein structure alignment using a genetic algorithm. Proteins 38, 428–440.PubMedCrossRefGoogle Scholar
  132. [132]
    Tagari, M., Tate, J., Swaminathan, G.J., Newman, R., Naim, A., Vranken, W., Kapopoulou, A., Hussain, A., Fillon, J., Henrick, K., Velankar, S. 2006. Emsd: Improving data deposition and structure quality. Nucleic Acids Res 34, D287–D290.PubMedCrossRefGoogle Scholar
  133. [133]
    Tanrikulu, Y., Schneider, G. 2008. Pseudoreceptor models in drug design: Bridging ligand- and receptor-based virtual screening. Nature Reviews Drug Discovery 7, 667–677.PubMedCrossRefGoogle Scholar
  134. [134]
    Taylor, W.R., Orengo, C.A. 1989. Protein structure alignment. Journal of Molecular Biology 208, 1–22.PubMedCrossRefGoogle Scholar
  135. [135]
    Tong, W., Williams, R.J., Wei, Y., Murga, L.F., Ko, J., Ondrechen, M.J. 2008. Enhanced performance in prediction of protein active sites with thematics and support vector machines. Protein Sci 17, 333–341.PubMedCrossRefGoogle Scholar
  136. [136]
    Tzakos, A.G., Grace, C.R., Lukavsky, P.J., Riek, R. 2006. Nmr techniques for very large proteins and rnas in solution. Annu Rev Biophys Biomol Struct 35, 319–342.PubMedCrossRefGoogle Scholar
  137. [137]
    Unger, R., 2004. The genetic algorithm approach to protein structure prediction. Structure and Bonding 110, 153–175.Google Scholar
  138. [138]
    Venkatachalam, C.M., Jiang, X., Oldfield, T., Waldman, M. 2003. Ligandfit: A novel method for the shape-directed rapid docking of ligands to protein active sites. J Mol Graph Model 21, 289–307.PubMedCrossRefGoogle Scholar
  139. [139]
    Venter, J.C., Adams, M.D., Myers, E.W., Li, P.W., Mural, R.J., Sutton, G.G., Smith, H.O., Yandell, M., Evans, C.A., Holt, R.A., Gocayne, J.D., Amanatides, P., Ballew, R.M., Huson, D.H., Wortman, J.R., Zhang, Q., Kodira, C.D., Zheng, X.H., Chen, L., Skupski, M., Subramanian, G., Thomas, P.D., Zhang, J., Gabor Miklos, G.L., Nelson, C., Broder, S., Clark, A.G., Nadeau, J., Mckusick, V.A., Zinder, N., Levine, A.J., Roberts, R.J., Simon, M., Slayman, C., Hunkapiller, M., Bolanos, R., Delcher, A., Dew, I., Fasulo, D., Flanigan, M., Florea, L., Halpern, A., Hannenhalli, S., Kravitz, S., Levy, S., Mobarry, C., Reinert, K., Remington, K., Abu-Threideh, J., Beasley, E., Biddick, K., Bonazzi, V., Brandon, R., Cargill, M., Chandramouliswaran, I., Charlab, R., Chaturvedi, K., Deng, Z., Di Francesco, V., Dunn, P., Eilbeck, K., Evangelista, C., Gabrielian, A.E., Gan, W., Ge, W., Gong, F., Gu, Z., Guan, P., Heiman, T.J., Higgins, M.E., Ji, R.R., Ke, Z., Ketchum, K.A., Lai, Z., Lei, Y., Li, Z., Li, J., Liang, Y., Lin, X., Lu, F., Merkulov, G.V., Milshina, N., Moore, H.M., Naik, A.K., Narayan, V.A., Neelam, B., Nusskern, D., Rusch, D.B., Salzberg, S., Shao, W., Shue, B., Sun, J., Wang, Z., Wang, A., Wang, X., Wang, J., Wei, M., Wides, R., Xiao, C., Yan, C. 2001. The sequence of the human genome. Science 291, 1304–1351.PubMedCrossRefGoogle Scholar
  140. [140]
    Wallace, C.J. 1993. Understanding cytochrome c function: Engineering protein structure by semisynthesis. FASEB J 7, 505–515.PubMedGoogle Scholar
  141. [141]
    Wang, Y., Xiao, Suzek, T.O., Zhang, J., Wang, J., Bryant, S.H. 2009. PubChem: A public information system for analyzing bioactivities of small molecules. Nucleic Acids Res 37, W623–W633.PubMedCrossRefGoogle Scholar
  142. [142]
    Watkins, H.A., Baker, E.N. 2006. Structural and functional analysis of rv3214 from mycobacterium tuberculosis, a protein with conflicting functional annotations, leads to its characterization as a phosphatase. Journal of Bacteriology 188, 3589–3599.PubMedCrossRefGoogle Scholar
  143. [143]
    Wuthrich, K. 2003. Nmr studies of structure and function of biological macromolecules. Biosci Rep 23, 119–168.PubMedCrossRefGoogle Scholar
  144. [144]
    Xiang, Z. 2006. Advances in homology protein structure modeling. Curr Protein Pept Sci 7, 217–227.PubMedCrossRefGoogle Scholar
  145. [145]
    Xie, L., Li, J., Xie, L., Bourne, P.E. 2009. Drug discovery using chemical systems biology: Identification of the protein-ligand binding network to explain the side effects of cetp inhibitors. PLoS Comput Biol 5, e1000387.PubMedCrossRefGoogle Scholar
  146. [146]
    Yeturu, K., Chandra, N. 2008. Pocketmatch: A new algorithm to compare binding sites in protein structures. BMC Bioinformatics 9, 543.PubMedCrossRefGoogle Scholar
  147. [147]
    Zhang, Y., Thiele, I., Weekes, D., Li, Z., Jaroszewski, L., Ginalski, K., Deacon, A.M., Wooley, J., Lesley, S.A., Wilson, I.A., Palsson, B., Osterman, A., Godzik, A. 2009. Three-dimensional structural view of the central metabolic network of thermotoga maritima. Science 325, 1544–1549.PubMedCrossRefGoogle Scholar
  148. [148]
    Zhu, J., Weng, Z. 2005. Fast: A novel protein structure alignment algorithm. Proteins 58, 618–627.PubMedCrossRefGoogle Scholar
  149. [149]
    Zoete, V., Michielin, O., Karplus, M. 2003. Proteinligand binding free energy estimation using molecular mechanics and continuum electrostatics. Application to hiv-1 protease inhibitors. Journal of Computer-Aided Molecular Design 17, 861–880.PubMedCrossRefGoogle Scholar

Copyright information

© International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Nagasuma Chandra
    • 1
  • Praveen Anand
    • 1
  • Kalidas Yeturu
    • 1
  1. 1.Bioinformatics CentreIndian Institute of ScienceBangaloreIndia

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