Molecular docking and binding interaction between psychedelic drugs and human serum albumin

Abstract

Drug-plasma protein interaction is a critical concern in monitoring drug circulation and drug-drug interactions. The present study aimed to investigate the interaction of psychedelic drugs such as lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), 2,5-dimethoxy-4-iodoamphetamine (DOI), psilocybin, psilocin, and mescaline with human serum albumin (HSA). The 3D structures of LSD, DMT, DOI, psilocybin, psilocin, mescaline, and albumin were obtained from the structural databases (www.rcsb.org, https://pubchem.ncbi.nlm.nih.gov/ compound). The structures were then prepared for molecular docking analysis by Autodock Vina software. Ultimately, the binding energies between docked HSA and psychedelic drugs were calculated, and their interactions were predicted. It was found that the psychedelic drugs can interact with HSA in the active site and the best minimum binding energies of !7.6 kcal/mol and !6.5 kcal/mol were shown by LSD and psilocybin, respectively. Our results indicated that all psychedelic drugs tested could interact with HSA at subdomains IA and IB. The structural properties of the drugs affect their interaction sites and binding energies. It was concluded that albumin, as the most abundant protein of the serum, could act as the biodistributor of psychedelic drugs.