Pharmacophore-based virtual screening and molecular dynamics simulations for identifying potential enamine inhibitors of bacterial CTX-M-14 β-lactamases
Year: 2025
Type: article
Abstract: CTX-M-14 β-lactamase is a key enzyme linked to antibiotic resistance, making it a critical target in infectious disease research. Here, a pharmacophore model based on known inhibitor interactions was used to virtually screen the Enamine antibacterial library. Top hits were docked into the CTX-M-14 active site using Glide, and filtered based on docking score, interaction quality, and ADMET properties. Lead compound E10 showed strong binding (GlideScore = −8.7 kcal/mol), excellent predicted oral absorption, low metabolic risk, and non-toxic excretion. Simulation studies showed that the CTX-M-14 and E10 complex remained stable. RMSF analysis indicated minimal fluctuations for most residues. E10 formed extensive hydrogen bonds with key active-site residues, providing strong polar stabilization. Cross-correlation analysis indicated cooperative residue dynamics were preserved. MM/GBSA calculations yielded a ΔG_bind of −58.89 kcal/mol, driven by favourable van der Waals and electrostatic interactions. These findings support E10 as a stable, high-affinity CTX-M-14 inhibitor suitable for further development.
Authors: Shafiul Haque, Farkad Bantun, Naif A. Jalal, Hani Faidah, Ahmad O. Babalghith, Abdullah F. Aldairi, Md. Tabish Rehman
Institutions: Universidad Espíritu Santo, Umm al-Qura University
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $944
OpenAlex ID: W7082251691