Title: Computational molecular docking and structural specificity of bipyrazoles as non-zinc chelating inhibitors of MMP-13

Authors: G. Nirmala; YesuBabu Adimulam; P. Seetharamaiah

Addresses: Department of Computer Science and Engineering, Sir C.R. Reddy College of Engineering, Eluru 534007, Andhra Pradesh, India ' Department of Computer Science and Engineering, Sir C.R. Reddy College of Engineering, Eluru 534007, Andhra Pradesh, India ' Department of Computer Science and Systems Engineering, Andhra University, Vishakapatnam 530003, Andhra Pradesh, India

Abstract: Matrix metalloproteinases (MMP) degrade extra cellular matrix proteins. Matrix MMPs are structurally similar, but differ in substrate specificity. A large number of MMP inhibitors have been described as zinc binding groups; however, in this paper we report computational identification of novel bipyrazoles as non-zinc chelating inhibitors of MMP-13. Molecular docking analysis performed between a set of 37 bipyrazoles vs. MMP-13 resulted in compound 26 observed with a score of −241 kcal/mol which is nearly half fold than the 456C bound ligand (−155.299 kcal/mol). The binding orientations of all bipyrazoles are geometrically similar to the co-crystallised ligand of 456C. Considering the distance (A°) between zinc atom and nearest N atom on pyrazole as well as Lipinski's rule of 5, compound 2 might act as a non-zinc chelating inhibitor.

Keywords: MMP inhibitors; matrix metalloproteinases; MMP-13; zinc binding groups; bipyrazoles; non-zinc chelating inhibitors; molecular docking; structural specificity; computational identification.

DOI: 10.1504/IJCBDD.2016.074988

International Journal of Computational Biology and Drug Design, 2016 Vol.9 No.1/2, pp.162 - 171

Received: 17 Jul 2015
Accepted: 06 Sep 2015

Published online: 28 Feb 2016 *

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