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Computational Characterization of Metal Binding Groups for Metalloenzyme Inhibitors
Journal article   Peer reviewed

Computational Characterization of Metal Binding Groups for Metalloenzyme Inhibitors

Kerwin D Dobbs, Amy M Rinehart, Michael H Howard, Ya-Jun Zheng and Daniel A Kleier
Journal of chemical theory and computation, v 2(4), pp 990-996
Jul 2006
PMID: 26633058

Abstract

The mode of action of many pest or disease control agents involves inhibition of some metalloenzyme that is essential for the survival of the target organism. These inhibitors typically consist of a functional group that is capable of a primary binding interaction with the metal and a scaffold that is capable of secondary interactions with the remainder of the enzyme. To characterize the binding ability of various metal binding groups (BGs), we have performed electronic structure calculations on ligand displacement reactions in a model system related to the metalloenzyme, peptide deformylase:  E-M-R + BG → E-M-BG + R. Here E represents a model coordination environment for the metal M, and R is a reference ligand (e.g., water) that may be displaced by a metal binding group. Since the oxidation state of many of the metals considered allows for multiple spin states, we also studied the influence of spin state on the coordination environment. Qualitative considerations of electronic structure inspired by the calculations provide an understanding of binding energy trends across a variety of ligands for a given metal and across a variety of metals for a given ligand.

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Collaboration types
Industry collaboration
Domestic collaboration
Web of Science research areas
Chemistry, Physical
Physics, Atomic, Molecular & Chemical
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