Molecular Mechanics/Coarse-grain simulations as a structural prediction tool for GPCRs/ligand complexes

G-protein coupled receptors (GPCRs) are the most common family of transmembrane receptors in humans. Bioinformatics-based approaches have provided accurate structural predictions of these proteins in complex with their agonist/antagonists when reliable template could be identified. Unfortunately, the average sequence identity across GPCR’s is in the majority of cases below 20%. In these cases, target selection and alignment required for homology modelling is nontrivial, and subsequent standard docking procedures may suffer from severe limitations. A hybrid “Molecular Mechanics/Coarse-Grained” (MM/CG) scheme, developed by some of us and reviewed here, has been shown to improve the quality of structural predictions in few cases and holds promises for high-throughput investigations of GPCR/ligand complexes which do not possess a highly reliable structural template.