Identification of phytochemical inhibitors targeting phosphate acetyltransferase of Mycoplasma genitalium: insights from virtual screening and molecular dynamics studies.

Abstract

Mycoplasma genitalium (M. genitalium) has evolved as a superbug, and the developing antimicrobial resistancewith just a few treatment options available is an imminentconcern. Due to the emergence of antibiotic resistance, a new antibiotic class or medications are requiredto combat this pathogen. The phosphate acetyltransferase (PTA) enzyme can be a suitable drug target which is essential for M. genitalium survival and involves in acetate metabolism. To efficiently find potent inhibitors, structure-based drug design approaches targeting the PTA of M. genitalium have been established. In this study, the three most potent phytochemical inhibitors were predicted from virtual screening and these are sitostanyl ferulate, beta-sitosterol-beta-D-glucoside, and brassinolide, with binding energies of - 9.66, - 9.60, and - 9.48kcal/mol, respectively. The active site residues Thr-125, Arg-300, Ser-299, Tyr-272, and Lys-273 appear to be critical in binding the three predicted potentinhibitors. The results of the molecular dynamics study indicate that the three predicted phytochemical inhibitors have formed stable bonds with PTA. Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) was utilized for the estimation of binding free energy of PTA-phytochemical complexes. Taken together, the findings of our computational work might aid in the development of possible potential drugsto treat and ameliorate the severity of M. genitalium infection.