Hybrid Molecular Mechanics/Coarse-Grained Simulations for Structural Prediction of G-Protein Coupled Receptor/ Ligand Complexes

MICHAEL LEGUÈBE (PRIMER AUTOR); CHUONG NGUYEN (PRIMER AUTOR); LUCIANA CAPECE (PRIMER AUTOR); ZUNG HOANG ; ALEJANDRO GIORGETTI; PAOLO CARLONI

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2012 vol. 7 p. 47332 - 47332

1932-6203

Understanding how ligands bind to G-protein coupled receptors (GPCRs) provides insights into a myriad of cell processes and is crucial for drug development. Here we extend a hybrid molecular mechanics/coarse-grained (MM/CG) approach applied previously to enzymes to GPCR/ligand complexes. The accuracy of this method for structural predictions is established by comparison with recent atomistic molecular dynamics simulations on the human β2 adrenergic receptor, a member of the GPCRs superfamily. The results obtained with the MM/CG methodology show a good agreement with previous all-atom classical dynamics simulations, in particular in the structural description of the ligand binding site. This approach could be used for high-throughput predictions of ligand poses in a variety of GPCRs.