Advances in Computational Techniques to Study GPCR–Ligand Recognition

G-protein-coupled receptors (GPCRs) are among the most intensely investigated drug targets. The recent revolutions in protein engineering and molecular modeling algorithms have overturned the research paradigm in the GPCR field. While the numerous ligand-bound X-ray structures determined have provided invaluable insights into GPCR structure and function, the development of algorithms exploiting graphics processing units (GPUs) has made the simulation of GPCRs in explicit lipid–water environments feasible within reasonable computation times. In this review we present a survey of the recent advances in structure-based drug design approaches with a particular emphasis on the elucidation of the ligand recognition process in class A GPCRs by means of membrane molecular dynamics (MD) simulations.

TrendsGPCRs are among the most intensely investigated drug targets.Recent numerous ligand-bound X-ray structures have provided invaluable insights into GPCR structure and function.Structural modeling of GPCR activation/inactivation promises to accelerate drug discovery in this field.