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Developed & Maintained by
BIF Centre,
Department of Biochemistry & Biophysics,
University of Kalyani, Kalyani,
Nadia-741 235,
West Bengal India.
The term "homology modeling", also called comparative modeling or template-based modeling (TBM), refers to modeling a protein 3D
structure using a known experimentally determined structure of a homologous protein as a template. A protein structure is always of great
assistance in the study of protein function, dynamics, interactions with ligands and other proteins, and even within pharmaceutical industry
in structure-based drug discovery and drug design. Homology modeling can provide the molecular biologists and biochemists with "low-
resolution" structures, which will contain sufficient information about the spatial arrangement of important residues in the protein and
which may guide the design of new experiments. For example, the design of site-directed mutagenesis experiments could be considerably
improved if such "low-resolution" model structures could be used.
Experimental elucidation of a protein structure may often be delayed by difficulties in obtaining a sufficient amount of protein (cloning,
expression and purification of milligram quantities), by difficulties associated with crystallization, and even the protein crystallographic part
may become a source of problems. In this context, it is not surprising that methods dealing with the prediction of protein structure have
gained much interest. Among these methods, the method of homology modeling usually provides the most reliable result. The use of this
method is based on the observation that two proteins belonging to the same family and sharing similar amino acid sequences will have
similar three-dimensional structures. By other words, the problem is reduced to finding a modeling template.
After finding a template it is an absolute requirement that before starting the modeling project, you make a multiple sequence alignment,
which should include your sequence, the sequence of the template and some other sequences of proteins belonging to the same family.
This will give you an overview of the general features of the protein family, the degree of conservation, the consensus sequence motifs, etc.
It would also be very desirable to make a secondary structure prediction, discussed in the tutorial on sequence alignment. Most importantly,
the positions of insertions and deletions should be correct, likewise the conservation of important residues, for example active site
residues. When the sequence analysis is done and the alignment is corrected accordingly, we may proceed to the modeling. The modeling
software will thread your sequence on the template structure, thus creating a preliminary model of you protein (backbone generation).
After that it will try to build missing parts, generate side chains for replaced residues and optimize side chain conformations, etc. At the last
step the overall model needs to be optimized followed by verification of model quality.


REFERENCE:
1. Chothia, C; Lesk, AM (1986). "The relation between the divergence of sequence and structure in proteins". EMBO J 5 (4): 823-6. PMC
1166865. PMID 3709526.

2. Kaczanowski, S; Zielenkiewicz, P (2010). "Why similar protein sequences encode similar three-dimensional structures?". Theoretical
Chemistry Accounts 125: 643-50.doi:10.1007/s00214-009-0656-3.

3. Peng, Jian; Jinbo Xu (2011). "RaptorX: Exploiting structure information for protein alignment by statistical inference". Proteins 79: 161-71.
doi:10.1002/prot.23175.PMC 3226909. PMID 21987485

4. Peng, Jian; Jinbo Xu (April 2011). "a multiple-template approach to protein threading".Proteins 79 (6): 1930-1939. doi:10.1002/prot.23016

5. Greer, J. (1981). "Comparative model-building of the mammalian serine proteases".Journal of Molecular Biology 153 (4): 1027-42.
doi:10.1016/0022-2836(81)90465-4

6. John, B; Sali, A. (2003). "Comparative protein structure modeling by iterative alignment, model building and model assessment". Nucleic
Acids Res 31 (14): 3982-92.doi:10.1093/nar/gkg460. PMC 165975. PMID 12853614

7. Sánchez, R; Sali, A. (1998). "Large-scale protein structure modeling of the Saccharomyces cerevisiae genome". Proc Natl Acad Sci USA 95
(23): 13597-13602.doi:10.1073/pnas.95.23.13597. PMC 24864. PMID 9811845

8. Gopal, S; Schroeder, M; Pieper, U; Sczyrba, A; Aytekin-Kurban, G; Bekiranov, S; Fajardo, JE; Eswar, N; Sanchez, R; et al. (2001). "Homology-
based annotation yields 1,042 new candidate genes in the Drosophila melanogaster genome". Nat Genet 27 (3): 337-40. doi:10.1038/85922.
PMID 11242120

9. Vasquez, M. (1996). "Modeling side-chain conformation". Curr Opin Struct Biol 6 (2): 217-21. doi:10.1016/S0959-440X(96)80077-7. PMID
8728654

10. Zhang, Y; Skolnick, J. (2005). "The protein structure prediction problem could be solved using the current PDB library". Proc. Natl. Acad.
Sci. USA 102 (4): 1029-34.doi:10.1073/pnas.0407152101. PMC 545829. PMID 15653774

Homology Modelling
University of Kalyani, Nadia, West-Bengal, India.
Bioinformatics Infrastructure Facility
A DBT (Govt. of India) Sponsored Facility.
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