Hybrid molecular mechanics/coarse-grained simulations for structural prediction of G-protein coupled receptor/ligand complexes

LUCIANA CAPECE; MICHAEL LEGUÈBE; CHUONG NGUYEN; ALEJANDRO GIORGETTI; PAOLO CARLONI

San Miguel de Tucuman

Congreso; XLI Reunión Anual de la Sociedad Argentina de Biofísica; 2012

Sociedad Argentina de Biofisica

P { margin-bottom: 0.08in; direction: ltr; color: rgb(0, 0, 0); }P.western { font-family: "Cambria"; font-size: 12pt; }P.cjk { font-family: "Times New Roman",serif; font-size: 12pt; }P.ctl { font-family: "Times New Roman",serif; font-size: 12pt; } 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.