Homology model-based virtual

Table 14.2 Effect of sequence identity on enrichments obtained by homology model based virtual screening.

Challenges of Homology Model-Based Virtual Screening... 

Thus, EcR LBD homology models based on vertebrate nuclear receptor crystal structures, although instructive for general architecture and residue replacement, are, owing to their low sequence identity, rather speculative when used for ligand docking or as tools for virtual screens [164],... 

If the sequence of a protein has more than 90% identity to a protein with known experimental 3D-stmcture, then it is an optimal case to build a homologous structural model based on that structural template. The margins of error for the model and for the experimental method are in similar ranges. The different amino acids have to be mutated virtually. The conformations of the new side chains can be derived either from residues of structurally characterized amino acids in a similar spatial environment or from side chain rotamer libraries for each amino acid type which are stored for different structural environments like beta-strands or alpha-helices. 

Bissantz C, Bernard P, Hibert M, Rognan D. Protein-based virtual screening of chemical databases. II. Are homology models of G-protein coupled receptors suitable targets Proteins Struct Funct Genet 2003 50 5-25. 

Evers A, Klebe G. Successful virtual screening for a submicromolar antagonist of the neurokinin-1 receptor based on a ligand-supported homology model. J Med Ghent 2004 47 5381-92. 

E., O Neill, A., Hine, H., Burton, M. S., Voigt, J. H., Abagyan, R A., Bayne, M. L., Monsma, F. J., Jr. (2008) Discovery of novel chemotypes to a G-protein-coupled receptor through ligand-steered homology modeling and structure-based virtual screening. J Med Chem 51, 581-588. 

---