Virtual screening and molecular dynamics simulations of phytochemicals targeting cofactor-independent phosphoglycerate mutase in antimicrobial-resistant Mycoplasma genitalium .

Autor: Barik K; Department of Bioinformatics, Central University of South Bihar, Gaya, 824236 India., Mandal P; Department of Bioinformatics, Central University of South Bihar, Gaya, 824236 India., Arya PK; Department of Bioinformatics, Central University of South Bihar, Gaya, 824236 India., Singh DV; Department of Bioinformatics, Central University of South Bihar, Gaya, 824236 India., Kumar A; Department of Bioinformatics, Central University of South Bihar, Gaya, 824236 India.
Jazyk: angličtina
Zdroj: 3 Biotech [3 Biotech] 2024 Oct; Vol. 14 (10), pp. 231. Date of Electronic Publication: 2024 Sep 11.
DOI: 10.1007/s13205-024-04082-8
Abstrakt: Mycoplasma genitalium (M. genitalium) poses a significant challenge in clinical treatment due to its increasing antimicrobial resistance. This study investigates alternative therapeutic approaches by targeting the cofactor-independent phosphoglycerate mutase (iPGM) enzyme with phytochemicals derived from ethnobotanical plants. In silico screening identified several promising inhibitors, with 2-carboxy-D-arabinitol demonstrating the highest binding affinity (- 9.77 kcal/mol), followed by gluconic acid (- 9.03 kcal/mol) and citric acid (- 8.68 kcal/mol). Further analysis through molecular dynamics (MD) simulations revealed insights into the binding mechanisms and stability of these phytochemicals within the iPGM active site. The MD simulations indicated initial fluctuations followed by stability, with intermittent spikes in RMSD values. The lowest RMSF values confirmed the stability of the ligand-protein complexes. Key residues, including Ser-61, Arg-188, Glu-62, Asp-397, and Arg-260, were found to play crucial roles in the binding and retention of inhibitors within the active pocket. These findings suggest that the identified phytochemicals could serve as novel antimicrobial agents against M. genitalium by effectively inhibiting iPGM activity.
Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest in the publication of this paper.
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Databáze: MEDLINE
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