Inferring the affinity and interactions of quercetin with Class C β-lactamase (AmpC, pdb code: 4HEF) by integrating molecular docking and molecular dynamics simulation approaches

Abstract

Introduction: Microbial drug resistance generated serious problems in treating infectious diseases and decreased the efficiency and efficacy of antibiotics. Investigating for inhibitors of these pathogens is helpful to decrease microbial resistance against antibiotics and to decrease high mortality rates due to the resistance of microorganisms. In this paper, quercetin, which is a natural compound with significant medicinal effects, can be used to inhibit AmpC β-lactamase class C enzymes.
Materials and Methods: Molecular docking and molecular dynamic simulation were performed to determine the binding pose, structural integrity, stability, and binding energy of class C β-lactamase with quercetin using Autodock 4.2.2 software and the GROMACS 2019.6 program applying the AMBER99SB force field, respectively.
Results: Molecular docking results and interaction analysis of molecular dynamics simulations indicated favorable hydrogen bonds and van der Waals interactions of quercetin with AmpC. These findings suggest that targeting β -lactamase using quercetin inhibitor analogs could provide a novel approach to treating antimicrobial resistance and could be used as a guide for future experimental studies.
Conclusion: By utilizing new molecular techniques, molecular docking, and molecular dynamics simulation, this paper suggests that quercetin, which has several medicinal effects, can be used to inhibit the AmpC- β-lactamase class C enzyme.