Title : Exploring the phytochemical based inhibition of PonA1 from Mycobacterium tuberculosis by molecular docking, dynamic simulation and ADMET studies

Abstract:

Objective: To perform molecular docking of plant-based bioactive compounds against a class of penicillin-binding protein PonA1 from Mycobacterium tuberculosis causing tuberculosis in humans. This study also authenticated the stable protein-ligand binding by molecular dynamic simulation.

Methods: The 3D structures of Withania somnifera (in Bengali Ashawagandha) phytochemicals, such as viscosalactone B, withaferin A and withanolide A, were retrieved from PubChem (https://pubchem.ncbi.nlm.nih.gov/), and were used as the ligands. The crystal structure of PonA1 (from  Mycobacterium tuberculosis) was selected as target, and was downloaded from RCSB Protein Data Bank (https://www.rcsb.org/), in 3D form. We have docked the phytochemical ligands to MtPonA1, and the protein-ligand interactions were analysed. Kanamycin was used as the control. The pharmacokinetics profile of the phytochemical ligands (viscosalactone B, withaferin A and withanolide A) were predicted in silico, and the structural authenticity of MtPonA1 was determined through Ramachandran plot analysis.  

Results: The docking analysis showed the highest binding affinity of withanolide A (binding energy −10.7 kcal/mol), followed by viscosalactone B (binding energy −9.2 kcal/mol) and withaferin A (−9.0 kcal/mol), against MtPonA1. The binding affinity of withanolide A to MtPonA1 was higher compared to the 2 other bioactive compounds, and hence the 'MtPonA1- withanolide A' complex and the free components of the docked complex (ligand and protein alone) were subjected to MDS, authenticating their stable binding, due to low binding free energy (−110.17 kJ/mol) with RMS deviation 0.15 nm and maximum RMS fluctuation 0.055 nm. Pharmacokinetics prediction revealed the acceptability of the ligands as drug-like compounds.

Conclusion: This in silico study suggests the usefulness of Withania somnifera derived bioactive chemical compounds as suitable leads to manage Mycobacterium tuberculosis infection causing deadly tuberculosis in humans.

Biography:

Dr. Shyamapada Mandal is Professor and Head of the Department of Zoology, and Dean (Science), University of Gour Banga, India. He is interested on infectious diseases, probiotics, and genomics and bioinformatics research. He did pre-PhD, PhD, and post-PhD research under the guidance of Professor Nishith Kumar Pal at Calcutta School of Tropical Medicine, India. He has published 118 articles with eight book chapters. He is life member of IAMM and IASR, India, and fellow member of SASS, India. Eight national academic and research awards have been conferred to him. He has guided 52 post graduate students; supervised three MPhil and three PhD students, and supervising 7 PhD and one MPhil students. Professor Mandal is among the world’s top 2% scientists as per the survey of the Stanford University, published in PLOS (Public Library of Science) Biology (October, 2020). He is featured in the top 2% world scientists list for second consecutive time as published by the Stanford University-Elsevier BV (October, 2021).