In silico docking and molecular dynamics simulation of 3-dehydroquinate synthase (DHQS) from Mycobacterium tuberculosis

Journal of Molecular Modeling
Mustafa Alhaji IsaShazia Haider

Abstract

The shikimate pathway is as an attractive target because it is present in bacteria, algae, fungi, and plants but does not occur in mammals. In Mycobacterium tuberculosis (MTB), the shikimate pathway is integral to the biosynthesis of naphthoquinones, menaquinones, and mycobactin. In these study, novel inhibitors of 3-dehydroquinate synthase (DHQS), an enzyme that catalyzes the second step of the shikimate pathway in MTB, were determined. 12,165 compounds were selected from two public databases through virtual screening and molecular docking analysis using PyRx 8.0 and Autodock 4.2, respectively. A total of 18 compounds with the best binding energies (-13.23 to -8.22 kcal/mol) were then selected and screened for absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, and nine of those compounds were found to satisfy all of the ADME and toxicity criteria. Among those nine, the three compounds-ZINC633887 (binding energy = -10.29 kcal/mol), ZINC08983432 (-9.34 kcal/mol), and PubChem73393 (-8.61 kcal/mol)-with the best binding energies were further selected for molecular dynamics (MD) simulation analysis. The results of the 50-ns MD simulations showed that the two compounds ZINC633887 and PubChem73393 formed ...Continue Reading

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Citations

Sep 14, 2019·Journal of Receptor and Signal Transduction Research·Goverdhan LankaSarita Rajender Potlapally
Feb 28, 2019·International Microbiology : the Official Journal of the Spanish Society for Microbiology·Kuifeng WangJiansheng Zhu
Oct 21, 2019·Computational Biology and Chemistry·Chaitanya Sadashiv JangamMd Ataul Islam

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