Molecular Docking, Dynamics Simulation, and Scanning Electron Microscopy (SEM) Examination of Clinically Isolated <i>Mycobacterium tuberculosis</i> by Ursolic Acid: A Pentacyclic Triterpenes

Abstract

The purpose of this study was to analyze the inhibitory action of ursolic acid (UA) as an antitubercular agent by computational docking studies and molecular dynamics simulations. The effect of UA on the cell wall of Mycobacterium tuberculosis (MTB) was evaluated by using Scanning Electron Microscopy (SEM). UA was used as a ligand for molecular interaction and investigate its binding activities to a group of proteins involved in the growth of MTB and the biosynthesis of the cell wall. Computational docking analysis was performed by using autodock 4.2.6 based on scoring functions. UA binding was confirmed by 30 ns molecular dynamics simulation using gromacs 5.1.1. H37Rv sensitive strain and isoniazid-resistant strain were used in the SEM study. UA showed to have the optimum binding affinity to inhA (Two-trans-enoyl-ACP reductase enzyme involved in elongation of fatty acid) with the binding energy of -9.2 kcal/mol. The dynamic simulation showed that the UA-inhA complex relatively stable and found to establish hydrogen bond with Thr196 and Ile194. SEM analysis confirms that UA treatment in both sensitive strain and resistant strain affected the morphology cell wall of MTB. This result indicated that UA could be one of the potential ligands for the development of new antituberculosis drugs.

Design of New Quinazoline Derivative as EGFR (Epidermal Growth Factor Receptor) Inhibitor through Molecular Docking and Dynamics Simulation

“…The advantage of molecular docking in designing a new inhibitor does not require a large amount of data or only employ some molecules as the lead compounds. Previous research had designed quinazoline derivative compounds by using quantitative structureactivity relationship (QSAR) analysis in large data compounds [16][17][18] and studied the stability of hydrogen bond formed through compound and protein [19][20][21][22]. However, designing a new EGFR inhibitor using a molecular docking approach of the lead compounds such as erlotinib, afatinib, and WZ4002 has never been done.…”

Regulation of Mitogen-Activated Protein Kinase Signaling Pathway and Proinflammatory Cytokines by Ursolic Acid in Murine Macrophages Infected with Mycobacterium avium

“…UA reportedly severely affected the cell wall peptidoglycan, and there were signs of cell wall damage distinguished in the H37Ra and H37Rv sensitive strain of MTB by using SEM and TEM. 5 , 6 This phenomenon is suspected to inhibit the interaction of Mycobacterium avium and macrophages from activating the signaling pathway that is responsible for the inhibition of the cytokine production.…”

“…Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of a sensitive MTB strain treated with UA revealed morphological abnormalities and lysis of cells. 5 , 6 Combination studies of UA and antituberculosis drugs (isoniazid, ethambutol, streptomycin, and rifampicin) also showed a synergistic effect in killing MTB. 7 …”

Molecular interactions of <i>Andrographis paniculata</i> Burm. f. Active Compound with Nuclear Receptor (CAR and PXR): An In Silico Assessment Approach

“…In silico molecular docking studies using Molecular Operating Environment (MOE) version 2010.10 (developed by Chemical Computing Group Inc, Canada), operated using HP 13-AN1033TU Notebook Windows 10 Home with an Intel® Core ™ i3-1005G1 processor with 512 GB SSD storage capacity and 8 GB memory. Molecular dynamics simulation to the molecular docking the result used AnteChamber PYthon Parser interfacE (ACPYPE), Gromacs 2016.3, g_mmpbsa package, and VMD 1.9.3 [26,27], which is operated using a computer with Intel (R) Core i5-8500 CPU@4.30GHz (6 CPUs) processor, 4096 MB RAM, 2 TB hard drive, 120 GB solidstate drive, NVIDIA GeForce GTX 1080 Ti.…”