Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors.

ABSTRACT: Following insights from recent crystal structures of the muscarinic acetylcholine receptor, binding modes of Positive Allosteric Modulators (PAMs) were predicted under the assumption that PAMs should bind to the extracellular surface of the active state. A series of well-characterized PAMs for adenosine (A₁ R, A_2A R, A₃ R) and muscarinic acetylcholine (M₁ R, M₅ R) receptors were modeled using both rigid and flexible receptor CHARMM-based molecular docking. Studies of adenosine receptors investigated the molecular basis of the probe-dependence of PAM activity by modeling in complex with specific agonist radioligands. Consensus binding modes map common pharmacophore features of several chemical series to specific binding interactions. Th

SUBMITTER: Sakkal LA 

PROVIDER: S-EPMC5403616 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature