Homology Model Versus X-ray Structure in Receptor-based Drug Design: A Retrospective Analysis with the Dopamine D3 Receptor.

ABSTRACT: Structure-based design methods commonly used in medicinal chemistry rely on a three-dimensional representation of the receptor. However, few crystal structures are solved in comparison with the huge number of pharmaceutical targets. This often renders homology models the only information available. It is particularly true for G protein-coupled receptors (GPCRs), one of the most important targets for approved medicines and current drug discovery projects. However, very few studies have tested their validity in comparison with corresponding crystal structures, especially in a lead optimization perspective. The recent solving of dopamine D3 receptor crystal structure allowed us to assess our historical homology model. We performed a statistical analysis, by docking our in-house lead optimizat

SUBMITTER: Levoin N 

PROVIDER: S-EPMC4018084 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature