title: Hybrid molecular mechanics/coarse-grained simulations for structural prediction of G-protein coupled receptor/ligand complexes.
abstract: 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.
authors.affiliation: INRIA Bordeaux Sud-Ouest, Institut de Mathématiques de Bordeaux, Talence, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Leguèbe
authors.forename: Chuong
authors.initials: C
authors.lastname: Nguyen
authors.forename: Luciana
authors.initials: L
authors.lastname: Capece
authors.forename: Zung
authors.initials: Z
authors.lastname: Hoang
authors.forename: Alejandro
authors.initials: A
authors.lastname: Giorgetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D001665:Binding Sites; D001696:Biomechanical Phenomena; D006801:Humans; D007545:Isoproterenol / Q000737:chemistry*; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011412:Propanolamines / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry*
chemical_list: D008024:Ligands; D008051:Lipid Bilayers; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; C014382:carazolol; D007545:Isoproterenol