Computational Insights into the Interaction of Muscimol with Human Serum Albumin

Abstract

Muscimol (MCM) is a psychoactive compound derived from the Amanita muscaria mushroom. It is known for its hallucinogenic properties and is primarily responsible for the psychoactive effects of the mushroom. The interaction of bioactive compounds with plasma transport proteins greatly affects their pharmacological profile and, thus, their potential therapeutic effects. Accordingly, using computational approaches, we investigated the interaction of MCM with the primary carrier protein in humans, human serum albumin (HSA). The preferred binding site of MCM is suggested at site III of HSA (binding energy: −6.56 kcal/mol), with sites I and II acting as less stable possible binding sites. Hydrogen bonds and van der Waals forces primarily contributed to stabilizing the MCM−HSA complexation, with possible involvement of ionic forces. An unfavorable interaction involving Ser-287 was identified as the cause of the reduced stability of MCM docking at site I.