Targeting thymidylate kinase of Mycoplasma genitalium with phytochemicals: insights from molecular docking and dynamics studies

利用植物化学物质靶向生殖支原体胸苷酸激酶:来自分子对接和动力学研究的启示

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Abstract

Mycoplasma genitalium (M. genitalium) has evolved into a superbug due to the emergence of antimicrobial resistance and is a growing concern with only a few treatment options. The emergence of antibiotic resistance has made it essential to create novel types of antibiotics or medications to treat this particular pathogen. The thymidylate kinase (tmk) enzyme may be a good drug target for M. genitalium survival as it is pivotal in DNA synthesis. Structure-based drug design approaches targeting tmk of M. genitalium have been established to find potent inhibitors efficiently. Phellodenol G, Phyllanthosterol, and stigmasterol were identified as the three most potent phytochemical inhibitors in this study, with binding energies of - 9.64, - 9.64, and - 9.54 kcal/mol, respectively. The active site residues Arg-53, Ser-101, and Leu-56 appear to be critical in the binding of potent inhibitors. As per molecular dynamics analysis, all three phytochemical inhibitors have stable interactions with tmk. MM-PBSA analysis indicates that phytochemical inhibitors are stable. Taken together, our computational findings may aid in the development of potential drugs to treat and mitigate the severity of M. genitalium infection (MGI).

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