Protein structure modeling using a homologous template is one of many routines that accompany the molecular dynamics simulation for biological material. There are currently two protocols of protein modeling available in Accelrys Discovery Studio 2.1, Build Mutants and Build Homology Modeling protocols. Both are template-based modeling, but with a different process. In this study, two different templates, 3CKZ and 274Y, have been used to see how much the differences will be made by those two protocols if the templates has significant percentage of identity. Evaluation of structure models has been performed using DOPE score, 3D-profile, and PROCHECK. The results indicated that Build Mutants Protocols produces more stable structures but has a low reliability values and low quality of stereochemistry when using a template that has a lower percentage of identity. The results also yield more stable, reliable, and higher percentage of residues in most favoured and additionally allowed region for the usage of Build Homology Modeling Protocol on both templates. These observations suggest that Build Homology Modeling protocol is recommended for protein modeling.
KeywordsProteinModelingMutationBuild Model Protocols
Kendrew, J. C., Bodo, G., Dintzis, H.M., Parrish, R.G., Wyckoff, H. and Phillips, D.C. (1958) A three-dimensional model of the myoglobin molecule obtained by x-ray analysis. Nature, 181, 662-666. doi:10.1038/181662a0
http://www.rcsb.org/pdb/statistics/holdings.do
Sali, A., Pottertone, L., Yuan, F., Van Vlijmen, H. and Karplus, M. (1995) Evaluation of comparative protein modeling by MODELLER. Proteins, 23, 318-326. doi:10.1002/prot.340230306
Lesk, A.M. and Chothia, C. (1986) The response of protein structures to amino-acid sequence changes. Philosophical Transactions of the Royal Society of London. Series A. Mathematical and Physical Sciences, 317, 345-356. doi:10.1098/rsta.1986.0044
Johnson, M.S., Srinivasan, N., Sowdhamini, R. and Blundell, T.L. (1994) Knowledge-based protein modeling. Critical Reviews in Biochemistry and Molecular Biology, 29, 168. doi:10.3109/10409239409086797
Congreve, M., Murray, C.W. and Blundell, T.L. (2005) Keynote review: Structural biology and drug discovery. Drug Discovery Today, 10, 895-907. doi:10.1016/S1359-6446(05)03484-7
Herlambang, S. J. and Saleh, R. (2011) Indonesian avian influenza H274Y mutant neuraminidase homology models assessment. Journal of Biophysical Chemistry, 2, 345-352. doi:10.4236/jbpc.2011.23039
http://www.pdb.org/pdb/home/home.do
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 Research, 25, 3389-3402. doi:10.1093/nar/25.17.3389
Zdobnov, E.M. and Apweiler, R. (2001) InterProScan—An integration platform for the signature-recognition methods in InterPro. Bioinformatics, 17, 847-848. doi:10.1093/bioinformatics/17.9.847
Arnold, K., Bordoli, L., Kopp, J. and Schwede, T. (2006) The SWISS-MODEL workspace: A web-based environment for protein structure homology modelling. Bioinformatics, 22, 195-201. doi:10.1093/bioinformatics/bti770
Kiefer, F., Arnold, K., Künzli, M., Bordoli, L. and Schwede, T. (2009) The SWISS-MODEL Repository and associated resources. Nucleic Acids Research, 37, 387-392. doi:10.1093/nar/gkn750
Schwede, T., Kopp, J., Guex, N. and Peitsch, M.C. (2003) SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Research, 31, 3381-3385. doi:10.1093/nar/gkg520
Guex, N. and Peitsch, M. C. (1997) SWISS-MODEL and the Swiss-Pdb Viewer: An environment for comparative protein modelling. Electrophoresis, 18, 2714-2723. doi:10.1002/elps.1150181505
Peitsch, M.C. (1995) Protein modeling by E-mail (From amino acid sequence to protein structure: A free one-hour service). Nature Biotechnology, 13, 658-660. doi:10.1038/nbt0795-658
Brooks, B.R., Bruccoleri, R.E., Olafson, B. D., States, D. J., Swaminathan, S. and Karplus, M. (1983) CHARMM: A program for macromolecular energy minimization and dynamics calculations. Journal of Computational Chemistry, 4, 187-217. doi:10.1002/jcc.540040211
Brooks, B.R., et al. (2009) CHARMM: The Biomolecular Simulation Program. Journal of Computational Chemistry, 30, 1545-1614.
Thompson, J.D., Higgins, D.G. and Gibson, T.J. (1994) CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic acids research, 22, 4673-4680. doi:10.1093/nar/22.22.4673
Henikoff, S. and Henikoff, J.G. (1992) Amino acid substitution matrices from protein blocks. Proceedings of the National Academy of Sciences of the USA, 89, 10915-10919. doi:10.1073/pnas.89.22.10915
Kabsch, W. and Sander, C. (1983) Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers, 22, 2577-2637. doi:10.1002/bip.360221211
Shen, M.-Y. and Sali, A. (2006) Statistical potential for assessment and prediction of protein structures. Protein Science, 15, 2507-2524.
Lüthy, R., Bowie, J.U. and Eisenberg, D. (1992) Assessment of protein models with three-dimensional profiles. Nature, 356, 83-85. doi:10.1038/356083a0
Ramachandran, G. N., Ramakrishnan, C. and Sasisekharan, V. (1963) Stereochemistry of polypeptide chain configuretions. Journal of Molecular Biology, 7, 95-99. doi:10.1016/S0022-2836(63)80023-6
Kabsch, W. and Sander, C. (1983) Biopolymers Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers, 22, 2577-2637. doi:10.1002/bip.360221211
Fiser, R.K. and Sali, A. (2000) Modeling of loops in protein structures. Protein Science, 9, 1753-1773. doi:10.1110/ps.9.9.1753
Laskowski, R.A., MacArthur, M.W., Moss, D.S. and Thornton, J.M. (1993) PROCHECK: A program to check the stereochemical quality of protein structures. Journal of Applied Crystallography, 26, 283-291. doi:10.1107/S0021889892009944
Morris, A.L., MacArthur, M.W., Hutchinson, E.G. and Thornton, J.M. (1992) Proteins: Structure, Function, and Bioinformatics. Biochemistry and Molecular Biology, 12, 345-364.
Chothia, C. and Lesk A.M. (1986) The relation between the divergence of sequence and structure in proteins. EMBO Journal, 5, 823-826.
Aloy, P., Ceulemans, H., Stark, A. and Russel, R.B. (2003) The relationship between sequence and interaction divergence in proteins. Journal of Molecular Biology, 332, 989-998. doi:10.1016/j.jmb.2003.07.006
Huang, C.W., Chen, Y.H., Chen, Y.H., Tsai, Y.C. and Lee, H.J. (2009) The interacton of Glu294 at the subunit interface is important for the activity and stability of goose δ-crystallin. Molecular Vision, 15, 2358-2363.
Kumar, M., Agarwal, T., Khokhar, S., Kumar, M., Kaur, P., Roy, T.S. and Dada, R. (2011) Mutation screening and genotype phenotype correlation of a-crystallin, g-crystallin and GJA8 gene in congenital cataract. Molecular Vision, 17, 693-707.
Biswas, D., Gupta, S.K., Sindhwani and Patras, A. (2009) TLR2 polymorphisms, Arg753GLn and Arg677Trp, are not associated with increased burden of tuberculosis in Indian patients. BMC Research Notes, 2, 162-167.
Zhang, J., Xue, F. and Chang, Y. (2008) Structural Determinants for Antagonist Pharmacology That Distinguish the ρ1GABAC Receptor from GABAA Receptor. Molecular Pharmacology, 74, 941-951. doi:10.1124/mol.108.048710
Patel, A., Dewangan, R., Khatri, S., Choubey, J., Gupta, S.K. and Verma, M.K. (2009) Identification of insilico 3D structure of amylase (Drosophila melanogaster) and comparative computational studies. Journal of Engineering and Technology Research, 1, 39-45.
Khatri, S., Patel, S., Choubey, J., Gupta, S.K. and Verma, M.K. (2010) Insilico 3D structure prediction of cell membrane associated protein ninjurin (homosapiens). Current Research Journal of Biological Sciences, 2, 1-5.
Satpathy, R., Guru, R.K., Behera, R. and Priyadarshini, A. (2010) Homology modelling of lycopene cleavage oxygenase: The key enzyme of bixin production. Journal of Computer Science of System Biology, 3, 59-61.
Singh, S., Kumar, A., Patel, A., Tripathi, A., Kumar, D. and Verma, D. (2010) In silico 3D structure prediction and comparison of nucleocapsid protein of H1N1. Journal of Modelling and Simulation of Systems, 1, 108-111.