Homology model-based virtual screening

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

Challenges of Homology Model-Based Virtual Screening... 

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. 

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. 

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],... 

The structure based virtual screening process includes also the use of some keywords. With these keywords FLAP fdters out matches and keeps them only if they make sense in terms of binding site shape. FLAP can also allow additional binding site volume (cavity expansion, useful when the protein structure under investigation is an homology model) and with the use of regions (definition of a sphere within each pharmacophore needs to have at least one point) or selection of a probe (enforcing a particular feature to be present in the calculated pharmacophores) certain constraints can also be added. 

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