Genome sequencing projects have resulted in a rapid increase in the number of known protein sequences. In contrast, only about one-hundredth of these sequences have been characterized using experimental structure determination methods. Computational protein structure modeling techniques have the potential to bridge this sequence-structure gap. This chapter presents an example that illustrates the use of MODELLER to construct a comparative model for a protein with unknown structure. Automation of similar protcols has resulted in models of useful accuracy for domains in more than half of all known protein sequences.
Keywords
- Protein Data Bank
- Consensus Model
- Protein Data Bank Code
- Multiple Template
- Multiple Structure Alignment
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, access via your institution.
Buying options
Springer Nature is developing a new tool to find and evaluate Protocols. Learn more
References
Baker, D., and Sali, A. (2001) Protein structure prediction and structural genomics. Science 294, 93–96.
Pieper, U., Eswar, N., Davis, F. P., Braberg, H., Madhusudhan, M. S., Rossi, A., Marti-Renom, M., Karchin, R., Webb, B. M., Eramian, D., Shen, M. Y., Kelly, L., Melo, F., and Sali, A. (2006) MODBASE: a database of annotated comparative protein structure models and associated resources. Nucleic Acids Res. 34, D291–295.
Marti-Renom, M. A., Stuart, A. C., Fiser, A., Sanchez, R., Melo, F., and Sali, A. (2000) Comparative protein structure modeling of genes and genomes. Annu. Rev. Biophys. Biomol. Struct. 29, 291–325.
Fiser, A., Do, R. K., and Sali, A. (2000) Modeling of loops in protein structures. Protein Sci. 9, 1753–1773.
Sali, A., and Blundell, T. L. (1993) Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779–815.
Eswar, N., Madhusudhan, M.S., Marti-Renom, M.A., Sali, A. (2005) BUILD_ PROFILE: a module for calculating sequence profiles in MODELLER. http://www.salilab.org/modeller
Marti-Renom, M. A., Madhusudhan, M. S., and Sali, A. (2004) Alignment of protein sequences by their profiles. Prot. Sci. 13, 1071–1087.
Eswar, N., Madhusudhan, M.S., Marti-Renom, M.A., Sali, A. (2005) PROFILE_ SCAN: A module for fold-assignment using profile-profile scanning in MODELLER. http://www.salilab.org/modeller
Madhusudhan, M. S., Marti-Renom, M. A., Sanchez, R., and Sali, A. (2006) Variable gap penalty for protein sequence-structure alignment. Protein Eng. Des. Sel. 19, 129–133.
MacKerell, A. D., Jr., Bashford, D., Bellott, M., Dunbrack, R. L., Jr., Evanseck, J. D., Field, M. J., Fischer, S., Gao, J., Guo, H., Ha, S., Joseph-McCarthy, D., Kuchnir, L., Muczera, K., Lau, F. T. K., Mattos, C., Michnik, S., Nguyen, D. T., Ngo, T., Prodhom, B., reiher, W. E., III, Roux, B., Schlenkrich, M., Smith, J. C., Stote, R., Straub, J., Watanabe, M., Wiorkiewicz-Kuczera, J., Yin, D., and Karplus, M. (1998) All-atom empirical potential for molecular modleing and dynamics studies of proteins. J.Phys.Chem.B. 102, 3586–3616.
Sali, A., and Overington, J. P. (1994) Derivation of rules for comparative protein modeling from a database of protein structure alignments. Protein Sci 3, 1582–1596.
Shen, M. Y., and Sali, A. (2006) Statistical potential for assessment and prediction of protein structures. Protein Sci. 15, 2507–2524.
Wu, G., Fiser, A., ter Kuile, B., Sali, A., and Muller, M. (1999) Convergent evolution of Trichomonas vaginalis lactate dehydrogenase from malate dehydrogenase. Proc. Natl. Acad. Sci. USA 96, 6285–6290.
Deshpande, N., Addess, K. J., Bluhm, W. F., Merino-Ott, J. C., Townsend-Merino, W., Zhang, Q., Knezevich, C., Xie, L., Chen, L., Feng, Z., Green, R. K., Flippen-Anderson, J. L., Westbrook, J., Berman, H. M., and Bourne, P. E. (2005) The RCSB Protein Data Bank: a redesigned query system and relational database based on the mmCIF schema. Nucleic Acids Res. 33, D233–237.
Smith, T. F., and Waterman, M. S. (1981) Identification of common molecular subsequences. J. Mol. Biol. 147, 195–197.
Needleman, S. B., and 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.
Madhusudhan, M. S., Eswar, N., Marti-Renom, M.A., Sali, A. (2005) SALIGN: A module for multiple sequence/structure alignments in MODELLER. http://www.salilab.org/modeller
John, B., and Sali, A. (2003) Comparative protein structure modeling by iterative alignment, model building and model assessment. Nucleic Acids Res. 31, 3982–3992.
Melo, F., Sanchez, R., and Sali, A. (2002) Statistical potentials for fold assessment. Protein Sci. 11, 430–448.
Rost, B. (1999) Twilight zone of protein sequence alignments. Protein Eng. 12, 85–94.
May, A. C. (2004) Percent sequence identity; the need to be explicit. Structure 12, 737–738.
Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., Zhang, Z., Miller, W., and Lipman, D. J. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402.
Pearson, W. R. (1998) Empirical statistical estimates for sequence similarity searches. J. Mol. Biol. 276, 71–84.
Henikoff, S., and Henikoff, J. G. (1992) Amino acid substitution matrices from protein blocks. Proc. Natl. Acad. Sci. USA 89, 10915–10919.
Zhou, H., and Zhou, Y. (2005) Fold recognition by combining sequence profiles derived from evolution and from depth-dependent structural alignment of fragments. Proteins 58, 321–328.
McGuffin, L. J., and Jones, D. T. (2003) Improvement of the GenTHREADER method for genomic fold recognition. Bioinformatics 19, 874–881.
Karchin, R., Cline, M., Mandel-Gutfreund, Y., and Karplus, K. (2003) Hidden Markov models that use predicted local structure for fold recognition: alphabets of backbone geometry. Proteins 51, 504–514.
Shi, J., Blundell, T. L., and Mizuguchi, K. (2001) FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties. J. Mol. Biol. 310, 243–257.
Dunbrack, R. L., Jr. (2006) Sequence comparison and protein structure prediction. Curr. Opin. Struct. Biol. 16, 374–384.
Xiang, Z. (2006) Advances in homology protein structure modeling. Curr. Protein Pept. Sci. 7, 217–227.
Sanchez, R., and Sali, A. (1997) Advances in comparative protein-structure modelling. Curr. Opin. Struct. Biol. 7, 206–214.
Eramian, D., Shen, M. Y., Devos, D., Melo, F., Sali, A., and Marti-Renom, M. A. (2006) A composite score for predicting errors in protein structure models. Protein Sci. 15, 1653–1666.
Jacobson, M. P., Pincus, D. L., Rapp, C. S., Day, T. J., Honig, B., Shaw, D. E., and Friesner, R. A. (2004) A hierarchical approach to all-atom protein loop prediction. Proteins 55, 351–367.
Fernandez-Fuentes, N., Oliva, B., and Fiser, A. (2006) A supersecondary structure library and search algorithm for modeling loops in protein structures. Nucleic Acids Res. 34, 2085–2097.
Zhu, K., Pincus, D. L., Zhao, S., and Friesner, R. A. (2006) Long loop prediction using the protein local optimization program. Proteins 65, 438–452.
Coutsias, E. A., Seok, C., Jacobson, M. P., and Dill, K. A. (2004) A kinematic view of loop closure. J. Comput. Chem. 25, 510–528.
van Vlijmen, H. W., and Karplus, M. (1997) PDB-based protein loop prediction: parameters for selection and methods for optimization. J. Mol. Biol. 267, 975–1001.
Sanchez, R., Sali, A. (1997) Evaluation of comparative protein structure modeling by MODELLER-3. Proteins 1, 50–58.
Srinivasan, N., and Blundell, T. L. (1993) An evaluation of the performance of an automated procedure for comparative modelling of protein tertiary structure. Protein Eng. 6, 501–512.
Sanchez, R., Sali, A. (1998) Large-scale protein structure modeling of the Saccharomyces cerevisiae genome. Proc. Natl. Acad. Sci. USA 95, 13597–13602.
Chothia, C., and Lesk, A. M. (1986) The relation between the divergence of sequence and structure in proteins. Embo. J. 5, 823–826.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Eswar, N., Eramian, D., Webb, B., Shen, MY., Sali, A. (2008). Protein Structure Modeling with MODELLER. In: Kobe, B., Guss, M., Huber, T. (eds) Structural Proteomics. Methods in Molecular Biology™, vol 426. Humana Press. https://doi.org/10.1007/978-1-60327-058-8_8
Download citation
DOI: https://doi.org/10.1007/978-1-60327-058-8_8
Publisher Name: Humana Press
Print ISBN: 978-1-58829-809-6
Online ISBN: 978-1-60327-058-8
eBook Packages: Springer Protocols