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Molecular modeling and virtual screening studies of NDM-1 Be | 16748
International Research Journals

International Research Journal of Biochemistry and Bioinformatics

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Molecular modeling and virtual screening studies of NDM-1 Beta lactamase for identification of a series of potent inhibitors.

Abstract

Randhawa Vinay and Jamwal Reema

NDM-1 metallo-�Ž�²-lactamase (class B) is a plasmid-borne zinc metalloenzyme that efficiently hydrolyzes �Ž�²-lactam antibiotics, including carbapenems, rendering them ineffective. Resistance to �Ž�² -lactam antibiotics mediated by metallo-�Ž�²-lactamases is an increasingly worrying clinical problem. Because NDM-1 has been found in several clinically important carbapenem-resistant pathogens, there is a need for inhibitors of this enzyme that could protect broad spectrum antibiotics from hydrolysis and thus extend their utility. In the presented research, the 3D structure of NDM-1 protein was modeled using homology modeling by Modeller9v5. Evaluation of the constructed NDM-1 protein model was done by PROCHECK, WHATCHECK, ERRAT, VERIYFY3D and through ProSA calculations. A compound library screening approach was used to identify compounds from the ZINC Database and characterize NDM-1 inhibitors from a library of active compounds. The strategy employed was divided into two categories, viz. screening and docking. A series of compounds from ZINC Database have been identified as potent inhibitors of NDM-1 metallo-�Ž�²-lactamase.

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