Comparative modeling is a powerful technique to generate models of proteins from families already represented by members with experimentally characterized three-dimensional structures. The method is particularly important for modeling membrane-bound receptors in the G Protein-Coupled Receptor (GPCR) family, such as many of the lipid receptors (such as the cannabinoid, prostanoid, lysophosphatidic acid, sphingosine 1-phosphate, and eicosanoid receptor family members), as these represent particularly challenging targets for experimental structural characterization methods. Although challenging modeling targets, these receptors have been linked to therapeutic indications that vary from nociception to cancer, and thus are of interest as therapeutic targets. Accurate models of lipid receptors are therefore valuable tools in the drug discovery and optimization phases of therapeutic development. This chapter describes the construction and evaluation of comparative structural models of lipid receptors beginning with the selection of template structures.

PMID:

 

22976030

 

[PubMed – indexed for MEDLINE]