Using protein homology models for structure-based studies: approaches to model refinement.
Homology modeling is a computational methodology to assign a 3-D structure to a target protein when experimental data are not available. The methodology uses another protein with a known structure that shares some sequence identity with the target as a template. The crudest approach is to thread the target protein backbone atoms over the backbone atoms of the template protein, but necessary refinement methods are needed to produce realistic models. In this mini-review anchored within the scope of drug design, we show the validity of using homology models of proteins in the discovery of binders for potential therapeutic targets. We also report several different approaches to homology model refinement, going from very simple to the most elaborate. Results show that refinement approaches are system dependent and that more elaborate methodologies do not always correlate with better performances from built homology models.
Kairys
V
V
Centro de Química da Madeira, Departamento de Química da Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal. kairys@uma.pt
Gilson
M K
MK
Fernandes
Miguel Xavier
MX
D019295:Computational Biology / Q000379:methods*; D015195:Drug Design; D008956:Models, Chemical; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship