Figure 3
From: Structural Basis for Binding of Allosteric Drug Leads in the Adenosine A1 Receptor
GaMD simulations predicted the A1AR PAM VCP171 recognized an allosteric site defined by extracellular loop 2 (ECL2): (A) Low-energy binding mode of VCP171 identified from dual-boost GaMD simulations using AMBER. The receptor, orthosteric agonist NECA and PAM VCP171 are shown in ribbons, spheres and sticks, respectively. Residues found within 5 Å of the bound VCP171 are highlighted in balls-and-sticks. (B–E) A1AR residues for which alanine substitution were shown in a previous structure-function study27 to significantly decrease (orange) or enhance (red) VCP171 affinity (B), binding cooperativity (C), efficacy (D) or functional cooperativity (E).
