IDENTIFICATION OF POTENTIAL SALMONELLA TYPHI BETA-LACTAMASE TEM 1 INHIBITORS USING PEPTIDOMIMETICS, VIRTUAL SCREENING, AND MOLECULAR DYNAMICS SIMULATIONS


Rakesh K. R. Pandit, Dinesh Gupta, Tapan K. Mukherjee

Abstract


Objective: The purpose of this study was to identify a potential peptidomimetic S. typhi Beta-lactamase TEM 1 inhibitor to tackle the antibiotic resistance among S. typhi.

Methods: The potential peptidomimetic inhibitor was identified by in silico docking of the small peptide WFRKQLKW with S. typhi Beta-lactamase TEM 1. The 3D coordinate geometry of the residues of small peptide interacting with the active site of the receptor was generated and mimics were identified using PEP: MMs: MIMIC server. All the identified mimics were docked at the active site of the receptor using Autodock 4.2 and the best-docked complex was selected on the basis of binding energy and number of H-bonds. The complex was then subjected to molecular dynamics simulations of 30 ns using AMBER 12 software package. The stereochemical stability of the Beta-lactamase TEM 1-WFRKQLKW complex was estimated with the help of Ramachandran plot using PROCHECK tool.

Results: In the present study, a new potential peptidomimetic inhibitor (ZINC05839264) of Beta-lactamase TEM 1 has been identified based on antimicrobial peptide WFRKQLKW by virtual screening of the MMsINC database. The docking and molecular simulation studies revealed that the mimic binds more tightly to the active site of the receptor than the peptide. The Ramachandran plot also shows that the Beta-lactamase TEM 1-mimic complex is stereo chemically more stable than Beta-lactamase TEM 1-WFRKQLKW complex as more number of residues (93.6%) are falling under the core region of the plot in case of the former.

Conclusion: The study shows that the peptidomimetic compound can act as a potential inhibitor of S. typhi Beta-lactamase TEM 1 and further it can be developed into more effective therapeutic to tackle the problem of antibiotic resistance.


Keywords


S. typhi, Beta-lactamase TEM 1, Antibiotic Resistance, Virtual screening, Docking, Peptidomimetics, Molecular dynamics simulation

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About this article

Title

IDENTIFICATION OF POTENTIAL SALMONELLA TYPHI BETA-LACTAMASE TEM 1 INHIBITORS USING PEPTIDOMIMETICS, VIRTUAL SCREENING, AND MOLECULAR DYNAMICS SIMULATIONS

Keywords

S. typhi, Beta-lactamase TEM 1, Antibiotic Resistance, Virtual screening, Docking, Peptidomimetics, Molecular dynamics simulation

DOI

10.22159/ijpps.2018v10i1.21520

Date

01-01-2018

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 10, Issue 1, 2018 Page: 91-96

Online ISSN

0975-1491

Authors & Affiliations

Rakesh K. R. Pandit
Department of Biotechnology, Chandigarh Group of Colleges, Landran, Mohali, Punjab
India

Dinesh Gupta
Translational Bioinformatics Group, International Centre of Genetic Engineering and Biotechnology, New Delhi
India

Tapan K. Mukherjee
Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Ambala
India


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