Identification of Novel DHFR Inhibitors for Klebsiella pneumoniae through Virtual Screening and Molecular Dynamics

Identification of Novel DHFR Inhibitors for Klebsiella pneumoniae through Virtual Screening and Molecular Dynamics | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 24 February 2025 V1 Latest version Share on Identification of Novel DHFR Inhibitors for Klebsiella pneumoniae through Virtual Screening and Molecular Dynamics Authors : Ihteshamul Haq , Shahina Akter 0000-0001-7776-6686 [email protected] , Faheem Anwar , and Yigang Tong Authors Info & Affiliations https://doi.org/10.22541/au.174038621.15642160/v1 218 views 123 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Dihydrofolate reductase (DHFR) is a critical enzyme for bacterial survival, catalyzing the reduction of folate to tetrahydrofolate (THF), a vital cofactor for DNA synthesis. The significant structural differences between bacterial and human DHFR present an opportunity for targeted drug discovery, especially in combating antibiotic resistance. This study employed virtual screening and molecular dynamics simulations to identify novel inhibitors of DHFR in Klebsiella pneumoniae. Three ligands, specifically 5, 16, and 25, were found to exhibit strong binding affinities within the folate-binding site, effectively competing with the natural substrate. Detailed analyses revealed that ligand 5 engages critical residues such as Met20 and Asp27, indicating a potential mechanism for competitive inhibition. Ligands 16 and 25 also demonstrated substantial interaction stability, disrupting substrate binding through diverse intermolecular forces. Molecular dynamics simulations indicated consistent stability metrics across root-mean-square deviation (RMSD), polar surface area (PSA), and solvent-accessible surface area (SASA) assessments, confirming robust binding characteristics. These findings suggest that ligands 5, 16, and 25 represent promising leads for the development of novel antibacterial agents targeting DHFR, with the potential to circumvent common resistance mechanisms. Future research will be essential to validate these compounds in vitro and in vivo, paving the way for optimized therapeutic options against multidrug-resistant pathogens. Supplementary Material File (final dhfr paper.docx) Download 4.17 MB Information & Authors Information Version history V1 Version 1 24 February 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords bacteriophages bioinformatics in silico analysis microbial genomics Authors Affiliations Ihteshamul Haq Beijing University of Chemical Technology College of Life Science and Technology View all articles by this author Shahina Akter 0000-0001-7776-6686 [email protected] Bangladesh Council of Scientific and Industrial Research View all articles by this author Faheem Anwar Tianjin University View all articles by this author Yigang Tong Beijing University of Chemical Technology College of Life Science and Technology View all articles by this author Metrics & Citations Metrics Article Usage 218 views 123 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ihteshamul Haq, Shahina Akter, Faheem Anwar, et al. Identification of Novel DHFR Inhibitors for Klebsiella pneumoniae through Virtual Screening and Molecular Dynamics. Authorea . 24 February 2025. 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