Repository of Research and Investigative Information

Repository of Research and Investigative Information

Baqiyatallah University of Medical Sciences

Molecular dynamics simulation (MDS) analysis of Vibrio cholerae ToxT virulence factor complexed with docked potential inhibitors

(2018) Molecular dynamics simulation (MDS) analysis of Vibrio cholerae ToxT virulence factor complexed with docked potential inhibitors. Bioinformation. pp. 101-105. ISSN 0973-8894

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Abstract

The ToxT transcription factor mediates the transcription of the two major virulence factors in Vibrio cholerae. It has a DNA binding domain made of alpha 4, alpha 5, alpha 6, alpha 7, alpha 8, alpha 9 and alpha 10 helices that is responsible for the transcription of virulence genes. Therefore, it is of interest to screen ToxT against the ZINC ligand database containing data for a million compounds. The QSAR model identified 40 top hits for ToxT. Two target protein complexes with ligands Lig N1 and Lig N2 with high score were selected for molecular dynamics simulation. Simulation data shows that ligands are stable in the DNA binding domain of ToxT. Moreover, Lig N1 and Lig N2 passed pharmacological as well as ADME filters along with g-mmpbsa analysis with binding affinity of -199.831 kJ/mol for Lig N1 and -286.951 kJ/mol for Lig N2. Moreover, no Lipinski and PhysChem violations were identified. It is further observed that these compounds were not inhibitors of P-glycoprotein, CYP450 and renal organic cation transporters. The LD50 of 2.5804 mol/kg for Lig N1 and 2.7788 mol/kg for Lig N2 was noted with acceptable toxicity index.

Item Type: Article
Keywords: ToxT Vibrio cholerae QSAR g-mmpbsa molecular dynamics simulation Mathematical & Computational Biology
Divisions:
Page Range: pp. 101-105
Journal or Publication Title: Bioinformation
Journal Index: ISI
Volume: 14
Number: 3
Identification Number: https://doi.org/10.6026/97320630014101
ISSN: 0973-8894
Depositing User: مهندس مهدی شریفی
URI: http://eprints.bmsu.ac.ir/id/eprint/3947

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