ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Virtual screening, docking, molecular dynamics study of efflux pump inhibitors against Helicobacter pylori

B. Akshaya Devi, Dhananjay Jade, K. H Sreenithya, Michael A. Harrison, and Shobana Sugumar

Department of Genetic Engineering, School of Bio-Engineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, India

E-mail: shobanas@srmist.edu.in

Received: 24 March 2024  Accepted: 25 September 2024

Abstract:

Helicobacter pylori is a Gram-negative bacterium that infects the human gastrointestinal mucosa and is a significant human pathogen, affecting 50% of the world’s population. Multidrug Efflux Pump mepA from the MATE family of proteins acts as a potential efflux pump target in Helicobacter pylori which exports multiple drugs outside the Helicobacter pylori and consists of 417 amino acids. This study aimed to identify potential inhibitors of the multidrug efflux pump mepA in Helicobacter pylori using in-silico approaches that employed molecular docking, drug-likeness evaluation, density functional theory [DFT], molecular dynamics (MD) simulations, and free energy calculations to analyze, the interactions between phytochemicals compounds and mepA protein. The best compounds exhibiting the highest binding affinities toward mepA were selected among all the screened phytochemical compounds from the database. Overall, this research identified three promising natural compounds Hinokiflavone (− 10.9 kcal/mol), Ipomine (− 10.7 kcal/mol), and Lupinisoflavone M (− 10.5 kcal/mol) from 30 top compounds based on binding affinity score, which demonstrated remarkable binding affinities toward mepA through molecular docking, suggesting their potential to block the efflux pump and potentiate antibiotic action with the potential to inhibit the multidrug efflux pump mepA in Helicobacter pylori. Besides, we select one complex for 3 compounds for an analysis of DFT and calculate the stability of protein and protein–ligand complex by Molecular Dynamics simulation along with this we calculate the binding free energy for the complex’s protein for selected Lupinisoflavone M complex (− 98.948 kJ/mol). The study highlights the promising capacity of the selected compounds to inhibit the mepA efflux pump, potentially paving the way for developing novel therapeutic strategies against multidrug-resistant pathogens.

Graphical abstract

Keywords: Helicobacter pylori; mepA; DFT analysis; MD simulation

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-024-03719-5

Chemical Papers 78 (16) 8889–8902 (2024)