Pharmacophore model-based virtual screening, docking, biological evaluation and molecular dynamics simulations for inhibitors discovery against <i>α</i>-tryptophan synthase from <i>Mycobacterium tuberculosis</i>

Naz, Sadia; Farooq, Umar; Khan, Sara; Sarwar, Rizwana; Mabkhot, Yahia N.; Saeed, Maria; Alsayari, Abdulrahman; Muhsinah, Abdullatif Bin; Ul-Haq, Zaheer

doi:10.1080/07391102.2020.1715259

Cited by 19 publications

(21 citation statements)

References 29 publications

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“…Promising or screened molecules from the ZINC database were saved in .pdb format using Marvin Sketch ( Akhmadiev et al, 2019). However, the top two hit molecules were further studied based on bioactive score Lohidakshan et al, 2018;Naz et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

Kumar

Kumari

Vishvakarma

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Coronavirus disease-2019 (COVID-19) is a global health emergency and the matter of serious concern, which has been declared a pandemic by WHO. Till date, no potential medicine/ drug is available to cure the infected persons from SARS-CoV-2. This deadly virus is named as novel 2019-nCoV coronavirus and caused coronavirus disease, that is, COVID-19. The first case of SARS-CoV-2 infection in human was confirmed in the Wuhan city of the China. COVID-19 is an infectious disease and spread from man to man as well as surface to man . In the present work, in silico approach was followed to find potential molecule to control this infection. Authors have screened more than one million molecules available in the ZINC database and taken the best two compounds based on binding energy score. These lead molecules were further studied through docking against the main protease of SARS-CoV-2. Then, molecular dynamics simulations of the main protease with and without screened compounds were performed at room temperature to determine the thermodynamic parameters to understand the inhibition. Further, molecular dynamics simulations at different temperatures were performed to understand the efficiency of the inhibition of the main protease in the presence of the screened compounds. Change in energy for the formation of the complexes between the main protease of novel coronavirus and ZINC20601870 as well ZINC00793735 at room temperature was determined on applying MM-GBSA calculations. Docking and molecular dynamics simulations showed their antiviral potential and may inhibit viral replication experimentally.

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Section: Methodsmentioning

confidence: 99%

Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

Kumar

Kumari

Vishvakarma

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…The final step in this pathway is catalyzed by tryptophan synthase and inhibition of this enzyme from M. tuberculosis (MtTRPS) with both previously known and novel TRPS inhibitors has been studied. [49][50][51][52][53][54] Inhibition of MtIGPS by novel compounds, however, remains largely unexplored. Yang and co-workers reported that MtIGPS is significantly inhibited by the antibiotics streptomycin, kanamycin, and geomycine.…”

Section: Inhibition Of Mtigpsmentioning

confidence: 99%

Indole‐3‐Glycerol Phosphate Synthase From Mycobacterium tuberculosis: A Potential New Drug Target

2021

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Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis, affects millions of people worldwide. Several TB drugs have lost efficacy due to emerging drug resistance and new anti-TB targets are needed. Recent research suggests that indole-3-glycerol phosphate synthase (IGPS) in M. tuberculosis (MtIGPS) could be such a target. IGPS is a (β/α) 8 -barrel enzyme that catalyzes the conversion of 1-(o-carboxyphenylamino)-1deoxyribulose 5'-phosphate (CdRP) into indole-glycerolphosphate (IGP) in the bacterial tryptophan biosynthetic path-way. M. tuberculosis over expresses the tryptophan pathway genes during an immune response and inhibition of MtIGPS allows CD4 T-cells to more effectively fight against M. tuberculosis. Here we review the published data on MtIGPS expression, kinetics, mechanism, and inhibition. We also discuss MtIGPS crystal structures and compare them to other IGPS structures to reveal potential structure-function relationships of interest for the purposes of drug design and biocatalyst engineering.

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“…[16][17][18] The closed conformation of the flexible α loop 6 (αL6) has a crucial role in ligand binding and catalytic activity of the TRPS α subunit. 15,19 Existing whole cell in vitro studies of compounds, specifically targeting α subunit have reported inhibition of bacterial growth. 13,19 The αβ interface portion of the indole channel has been identified to be the putative binding site of three potent inhibitors of bacterial TRPS which was supported by structural data.…”

Section: Introductionmentioning

confidence: 99%

“…15,19 Existing whole cell in vitro studies of compounds, specifically targeting α subunit have reported inhibition of bacterial growth. 13,19 The αβ interface portion of the indole channel has been identified to be the putative binding site of three potent inhibitors of bacterial TRPS which was supported by structural data. 6,[20][21][22] A photochromic azobenzene inhibitor of TRPS was identified, albeit its exact position was not resolved in the crystal structure of the complex.…”

Section: Introductionmentioning

confidence: 99%

Discovery of antimicrobial agent targeting tryptophan synthase

Bosken

Hilario

et al. 2021

Protein Science

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Pharmacophore model-based virtual screening, docking, biological evaluation and molecular dynamics simulations for inhibitors discovery against α-tryptophan synthase from Mycobacterium tuberculosis

Cited by 19 publications

References 29 publications

Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

Indole‐3‐Glycerol Phosphate Synthase From Mycobacterium tuberculosis: A Potential New Drug Target

Discovery of antimicrobial agent targeting tryptophan synthase

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