Structure-Based Screening of Non-β-Lactam Inhibitors against Class D β-Lactamases: An Approach of Docking and Molecular Dynamics

Divya Gupta; Aditi Singh; Pallavi Somvanshi; Ajeet Singh; Asad U Khan

doi:10.1021/acsomega.0c00356

Structure-Based Screening of Non-β-Lactam Inhibitors against Class D β-Lactamases: An Approach of Docking and Molecular Dynamics

ACS Omega. 2020 Apr 1;5(16):9356-9365. doi: 10.1021/acsomega.0c00356. eCollection 2020 Apr 28.

Authors

Divya Gupta^{1

2}, Aditi Singh³, Pallavi Somvanshi³, Ajeet Singh⁴, Asad U Khan^{1

5}

Affiliations

¹ Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202 002, India.
² Department of Life Sciences, Uttarakhand Technical University, Dehradun 248007 Uttarakhand, India.
³ Department of Biotechnology, TERI School of Advanced Studies, New Delhi 110070, India.
⁴ Department of Biotechnology, G. B. Pant Engineering College, Pauri 246194, India.
⁵ Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Terengganu 21030, Malaysia.

Abstract

The manifestation of class D β-lactamases in the community raises significant concern as they can hydrolyze carbapenem antibiotics. Hence, it is exceptionally alluring to design novel inhibitors. Structure-based virtual screening using docking programs and molecular dynamics simulations was employed to identify two novel non-β-lactam compounds that possess the ability to block different OXA variants. Furthermore, the presence of a nonpolar aliphatic amino acid, valine, near the active site serine, was identified in all OXA variants that can be accounted to block the catalytic activity of OXA enzymes.