Paper Citing NAMD - Abstract
Vaidehi, Nagarajan; Pease, James E.; Horuk, Richard
MODELING SMALL MOLECULE-COMPOUND BINDING To G-PROTEIN-COUPLED RECEPTORS
CHEMOKINES, PT A, 460:263-+, 2009
G-protein-coupled receptors (GPCRs) form a superfamily of membrane proteins that play a crucial role in mediating physiological processes as well as pathogenesis of many critical diseases. They are one of the most successful drug targets, accounting for more than 30% of prescription drugs on the market today. Three-dimensional structural information on GPCRs will greatly aid the drug design process, and great strides are being made in obtaining crystallographic information on GPCRs. Since this process is both tedious and risky, a combination of computational methods and biophysical experiments is a useful approach to rapidly obtain information on a wide variety of GPCRs. in this review, we describe the methods/protocols involved in these computational techniques, as well as methods for site-directed mutagenesis and ligand-binding assays that are currently being used for validating structural-model and small-molecule-ligand binding to GPCRs. We discuss the merits and pitfalls of the various methods used in obtaining structural and dynamic information for ligand binding to GPCRs. Another important factor to consider in drug design is the conformational flexibility of GPCRs since it has been shown that small-molecule ligands of varied efficacy stabilize different receptor conformations leading to functional selectivity of ligands. We discuss the computational methods used to study this specific ligand-induced state.
