Journal Article

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

Capece, Luciana, Leguèbe, Michael, Hoang, Zung, Giorgetti, Alejandro, Carloni, Paolo, Nguyen, Chuong

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adrenergic receptors / Analysis / Binding Sites / Biology / Biomechanical Phenomena / Biophysics / Chemistry / Coarsening / Coordination compounds / Coupling (molecular) / Drug development / Enzymes / G protein-coupled receptors / G proteins / Humans / Hydration / Isoproterenol - chemistry / Ligand binding (Biochemistry) / Ligands / Lipid Bilayers - chemistry / Lipids / Mechanics (physics) / Molecular dynamics / Molecular Dynamics Simulation / Molecular mechanics / Propanolamines - chemistry / Protein Binding / Protein Structure, Tertiary / Proteins / Receptors / Receptors, Adrenergic, beta-2 - chemistry / Simulation