Figure 2
From: Structural Basis for Binding of Allosteric Drug Leads in the Adenosine A1 Receptor
GaMD simulations predicted the A1AR PAM PD81723 recognized an allosteric site defined by extracellular loop 2 (ECL2): (A–C) Low-energy binding modes of PD81723 identified from (A) dual-boost GaMD simulations using AMBER, (B) dual-boost GaMD simulations using NAMD and (C) dihedral-boost GaMD simulations using NAMD. The receptor, orthosteric agonist NECA and PAM PD81723 are shown in ribbons, spheres and sticks, respectively. Residues found within 5 Å of the bound PD81723 are highlighted in balls-and-sticks. (D–G) A1AR residues for which alanine substitution were shown in a previous structure-function study27 to significantly decrease (orange) or enhance (red) PD81723 affinity (D), binding cooperativity (E), efficacy (F) or functional cooperativity (G).
