Figure 4
From: Structural Basis for Binding of Allosteric Drug Leads in the Adenosine A1 Receptor
PD81723 stabilized NECA binding within the A1AR orthosteric site: (A–C) structural clusters of NECA identified in simulations of the “A1AR + NECA” system using (A) dual-boost GaMD with AMBER, (B) dual-boost GaMD with NAMD and (C) dihedral-boost GaMD with NAMD. (D–F) structural clusters of NECA identified in simulations of the “A1AR + NECA + PD81723” system with no PD81723 bound at the ECL2 allosteric site using (D) dual-boost GaMD with AMBER, (E) dual-boost GaMD with NAMD and (F) dihedral-boost GaMD with NAMD. (G–I) structural clusters of NECA identified in simulations of the “A1AR + NECA + PD81723” system with PD81723 bound at the ECL2 allosteric site using (G) dual-boost GaMD with AMBER, (H) dual-boost GaMD with NAMD and (I) dihedral-boost GaMD with NAMD. The receptor, orthosteric agonist (NECA) and PAM (PD81723) are shown in ribbons, sticks and spheres, respectively. NECA clusters are colored by the potential of mean force (PMF) in a green(0 kcal/mol)-white-red(8 kcal/mol) scale and the NECA conformation extracted from the 2YDV X-ray structure of the A2AAR with two receptor transmembrane domains aligned is shown in orange for reference.
