Ligand docking to the acidic pocket of the proton-gated ion channel ASIC1a

Proton-gated ion channels of ASIC family play important role in many physiological and pathological processes and represent a perspective target for pharmacological modulation. Recently, atomic-scale structures of ASICs in closed, open and desensitized states have become available. This opened a possibility to model binding of ligands, which modulate ASIC activation and desensitization and to predict structures of new specifically acting pharmacological agents. In the present work we performed in docking of a series of ligands, which stabilize open or closed state of ASIC1a. For the first time we revealed a correlation between the spatial ligand structure and its mode of action. We revealed specific interactions of these inhibitors and potentiators with amino-acid residues in the acidic pocket of ASIC1a. The results allow predictive design of new drugs.