Zubrzycki, I and Blatch, Gregory ORCID: 0000-0003-0778-8577 (2001) DFT study of a substrate and inhibitors of 1-deoxy-2-xylulose-5-phosphate reductoisomerase - the potential novel target molecule for anti-malaria drug development. Journal of Molecular Modeling, 7 (10). pp. 378-383. ISSN 1610-2940

Abstract

1-Deoxy-2-xylulose-5-phosphate (DOXP) reductoisomerase is a novel target for developing anti-malaria drugs. The determination of structural and electronic properties of the inhibitor molecules is of crucial importance for analyzing the interactions between DOXP-reductoisomerase and its inhibitors. Geometry-optimizations and single point calculations at the B3LYP/3-21G*//B3LYP/3-21G** and B3LYP/3-21G*//MP2/3-21G** levels were performed to determine the structures and charge distributions of an enzyme substrate (1-deoxy-D-xylulose 5-phosphate) and the two inhibitors (fosmidomycin and FR-900098). The theoretically derived bond lengths are in excellent agreement with the corresponding experimental values reported for similar structures. Partial charges and dipole moments are assigned using the Mulliken and natural population analyses. The calculated structures and partial charge distributions can readily be used for the further development of biologically active inhibitors of DOXP-reductoisomerase as well as parameters for docking experiments.

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