Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811


Inhibitor and Substrate Binding by New Delhi metallo-beta-lactamase-1: A Molecular Dynamics Studies

Author(s): Yeng-Tseng Wang, Chi-Yu Lu, Tzyh-Chyuan Hour, Tian-Lu Cheng.


The control of beta-lactam antibiotics released through the inhibition of the New Delhi metallo-beta-lactamase 1 (NDM-1) has been identified as a potential target for the treatment of the muti-drugs resistance (MDR) bacteria disease. We have employed molecular dynamics (MD), alanine-scanning mutagenesis and molecular docking techniques to optimize the x-ray NDM-1 structure with 11 drugs (Tigecycline, BAL30072, D-captopril, Penicillin G, Ampicillin, Carbenicillin, Cephalexin, Cefaclor, Nitrocefin, Meropenem, and Imipenem). From our simulations, we found that the 5 residues Asp223, His120, His122, His162 and His189 are responsible for the selectivity of NDM-1 associated drugs.

Keywords: Alanine-scanning mutagenesis, molecular docking, molecular dynamics (MD), multi-drugs resistance (MDR), New Delhi metallo-beta-lactamase 1 (NDM-1), solvated interaction energies (SIE).

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Article Details

Year: 2014
Page: [197 - 204]
Pages: 8
DOI: 10.2174/1574886309666141126145225
Price: $58