Exploring Covalent Docking Mechanisms of Boron-Based Inhibitors to Class A, C and D β-Lactamases Using Time-dependent Hybrid QM/MM Simulations.

ABSTRACT: Recently, molecular covalent docking has been extensively developed to design new classes of inhibitors that form chemical bonds with their biological targets. This strategy for the design of such inhibitors, in particular boron-based inhibitors, holds great promise for the vast family of β-lactamases produced, inter alia, by Gram-negative antibiotic-resistant bacteria. However, the description of covalent docking processes requires a quantum-mechanical approach, and so far, only a few studies of this type have been presented. This study accurately describes the covalent docking process between two model inhibitors - representing two large families of inhibitors based on boronic-acid and bicyclic boronate scaffolds, and three β-lactamases which belong to the A, C, and D classes. Mol

SUBMITTER: Charzewski L 

PROVIDER: S-EPMC8380965 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature