Computational Modeling of Structure-Function of G Protein-Coupled Receptors with Applications for Drug Design

G protein-coupled receptors (GPCRs) mediate senses such as odor, taste, vision, and pain in mammals. In addition, important cell recognition and communication processes often involve GPCRs. Many diseases involve malfunction of GPCRs, making them important targets for drug development. Indeed, greater than 50 % of all marketed therapeutics act on those receptors. Unfortunately, the atomic-level structures are only available for rhodopsin, β2AR, β1AR, A2A adenosin and opsin. In silico computational methods, employing receptor-based modeling, offer a rational approach in the design of drugs targeting GPCRs. These approaches can be used to understand receptor selectivity and species specificity of drugs that interact with GPCRs. This review gives an overview of current computational approaches to GPCR model building; ligand-receptor interaction for drug design; and molecular mechanism of GPCR activation from simulation.