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Title |
Molecular dynamics simulation (MDS) analysis of Vibrio cholerae ToxT virulence factor complexed with docked potential inhibitors
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Authors |
Ibrahim Torktaz, Ali Najafi*, Reza Golmohamadi, Sorour Hassani
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Affiliation |
1Molecular Biology Research Center, Systems Biology and Poisonings institute, Baqiyatallah University of Medical Sciences, Tehran, IRAN;
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najafi74@bmsu.ac.ir; najafi74@yahoo.com;
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Article Type |
Hypothesis
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Date |
Received February 11, 2018; Revised February 28, 2018; Accepted February 28, 2018; Published March 31, 2018
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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 α4, α5, α6, α7, α8, α9 and α10 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.
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Keywords |
ToxT, Vibrio cholerae, QSAR, g-mmpbsa, molecular dynamics simulation
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Citation |
Torktaz et al. Bioinformation 14(3): 101-105 (2018)
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Edited by |
P Kangueane
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ISSN |
0973-2063
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Publisher |
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License |
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.
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