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Volume 6 (2006), Pages 1542-1554
Mini-Review Article

Using Protein Homology Models for Structure-Based Studies: Approaches to Model Refinement

1Centro de Química da Madeira, Departamento de Química da Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal
2Center for Advanced Research in Biotechnology, 9600 Gudelsky Drive, Rockville, MD 20850, USA

Received 15 July 2006; Revised 12 October 2006; Accepted 17 October 2006

Academic Editor: Miguel Augusto Rico Botas Castanho

Copyright © 2006 Miguel Xavier Fernandes et al.


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.