Molecular Docking and ADMET Profiling of Stigmasterol for Evaluating Its Antimicrobial Potential

Abstract

Due to development of resistance against antimicrobial agents, there arises a difficulty in treating microbial infections. Stigmasterol, also referred to as stigmasterin, is an unsaturated plant sterol found in several medicinal plants and has been reported in literature to exhibit antimicrobial activity. This study aims to evaluate the binding affinity of stigmasterol with multiple target proteins of Staphylococcus aureus and to assess its ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties. Rigid molecular docking was employed to determine the binding affinities. The 3D structures of six S. aureus proteins were retrieved from the Protein Data Bank, while the stigmasterol molecule was obtained from PubChem. ADMET profiling was performed using the SwissADME web tool, and molecular docking was conducted using PyRx software, incorporating AutoDock Vina (version 1.5.6). The target proteins studied included dihydrofolate reductase (PDB ID: 2W9S), DNA gyrase (PDB ID: 3U2D), dehydrosqualene synthase (PDB ID: 2ZCO), ketopantoate reductase (PDB ID: 4YCA), diphosphate synthase (PDB ID: 4H8E), and sortase A (PDB ID: 1T2P). The corresponding docking scores were -9.1, -8.5, -8.4, -8.3, -7.4, and -7.4 kcal/mol, respectively. The 2D interaction profiles of stigmasterol with these proteins were visualized using BIOVIA Discovery Studio 2021. In summary, Stigmasterol compound exhibits promising results based on the in-silico studies in comparison with the standard drug Oxacillin and ADMET studies were reported. ADMET studies shown that molecular docking with four proteins has shown good binding affinity score with Stigmasterol i.e.-9.1, -8.5, -8.4, -8.3 compared to standard drug with -8.0.