Interaction Mechanism of the Natural Product Falcarindiol and Human GABA(Delta) Receptor

Falcarindiol is a natural polyacetylene alcohol compound that has demonstrated anti-inflammatory, neurological and potentially anticancer properties, and modulates the activity of the gamma-aminobutyric acid type A(GABAA) receptor which is an important therapeutic target for neurological disorders in humans, but the mechanism of action is not clear. In this paper, the binding mode and dynamic properties of falcarindiol acting on GABAA receptor were investigated by molecular dynamics simulation, umbrella sampling simulations, binding free energy calculations and molecular docking, and determined that all three effective binding sites have antagonistic effects on this receptor. This work will provide a theoretical basis for the subsequent study of the effects of polyethynyl alcohol analogues on GABAA receptors and the corresponding drug development.