抄録
Objective: The purpose of this study was to analyze the inhibitory action of ursolic acid (UA) as antitubercular agent by computational docking studies and molecular dynamics simulations. The effect of UA against cell wall of Mycobacterium tuberculosis (MTB) was evaluated by using Scanning Electron Microscopy (SEM).
Methods: UA were used as ligand for molecular interaction and investigate its binding activities to group of enzymes involved in the biosynthesis of cell wall, biosynthesis of coenzyme A that essential for the growth of MTB, and biosynthesis of protein essential of MTB.The crystalographic structures of all molecular target were retrieved from RCSB Protein Data Bank (PDB). Computational docking analysis were performed using autodock 4.6 based on scoring functions. UA binding were confirmed by 30 ns molecular dynamics simulation using gromacs 5.1.1. H37Rv sensitive strain and INH resistant strain were used as strains in SEM study.
Results: UA showed to have the optimum binding affinity to inhA (enzyme in FAS II system that involved in the biosynthesis of cell wall) with the binding energy of -9.2 kcal/mol as compared to the standard isonicotinic-acyl NADH (-5.4 kcal/mol). Dynamic simulations showed that the conformation between UA and inhA relatively stable and found to establish hydrogen bound with Thr196 and Ile194. SEM analysis confirm that UA treatment in both sensitive strain and resistant strain affected the morphology cell wall of MTB.
Conclusion: This result indicated that UA could be one of the potential ligand for the development of new antituberculosis drugs.
