In silico identification of potential inhibitors against shikimate dehydrogenase through virtual screening and toxicity studies for the treatment of tuberculosis

International Microbiology : the Official Journal of the Spanish Society for Microbiology
Mustafa Alhaji IsaShazia Haider

Abstract

The present study attempts to identify the novel inhibitors of shikimate dehydrogenase (SD), the enzyme that catalyzes the fourth reaction in the shikimate pathway, through virtual screening and toxicity studies. Crystal structure of SD was obtained from Protein Data Bank (PDB ID 4P4G, 1.7 Å) and subjected to energy minimization and structure optimization. A total of 13,803 compounds retrieved from two public databases and used for the virtual screening based on physicochemical properties (Lipinski rule of five) and molecular docking analyses. A total of 26 compounds with good AutoDock binding energies values ranging between - 12.03 and - 8.33 kcal/mol was selected and further filtered for absorption distribution metabolism excretion and toxicity analyses (ADMET). In this, eight compounds were selected, which satisfied all the ADME and toxicity analysis properties. Three compounds with better AutoDock binding energies values (ZINC12135132, - 12.03 kcal/mol; ZINC08951370, - 10.04 kcal/mol; and ZINC14733847, 9.82 kcal/mol) were considered for molecular dynamic (MD) simulation and molecular generalized born surface area (MM-GBSA) analyses. The results of the analyses revealed that the two ligands (ZINC12135132 and ZINC08951370) ha...Continue Reading

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Citations

Mar 15, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·José E S NunesRodrigo G Ducati

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Software Mentioned

DataWarrior
MM
Chimera
Chiron
GBSA
Amber14
ff12SB
Ligplot +
Data warrior
Pymol

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