Identification of Novel Inhibitors of Type-I Mycobacterium Tuberculosis Fatty Acid Synthase Using Docking-Based Virtual Screening and Molecular Dynamics Simulation

Mycobacterial fatty acid synthase type-I (FAS-I) has an important role in the de novo synthesis of fatty acids, which constitute a major component of the cell wall. The essentiality of FAS-I in the survival and growth of mycobacterium makes it an attractive drug target. However, targeted inhibitors...

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Main Authors: Nidhi Singh, Shi-Qing Mao, Wenjin Li
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/11/15/6977
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author Nidhi Singh
Shi-Qing Mao
Wenjin Li
author_facet Nidhi Singh
Shi-Qing Mao
Wenjin Li
author_sort Nidhi Singh
collection DOAJ
description Mycobacterial fatty acid synthase type-I (FAS-I) has an important role in the de novo synthesis of fatty acids, which constitute a major component of the cell wall. The essentiality of FAS-I in the survival and growth of mycobacterium makes it an attractive drug target. However, targeted inhibitors against Mycobacterial FAS-I have not been reported yet. Recently, the structure of FAS-I from Mycobacterium tuberculosis was solved. Therefore, in a quest to find potential inhibitors against FAS-I, molecular docking-based virtual screening and molecular dynamics simulation were done. Subsequently, molecular dynamic simulations based on binding free energy calculations were done to gain insight into the predicted binding mode of putative hits. The detailed analysis resulted in the selection of four putative inhibitors. For compounds BTB14738, RH00608, SPB02705, and CD01000, binding free energy was calculated as −72.27 ± 12.63, −68.06 ± 11.80, −63.57 ± 12.22, and −51.28 ± 13.74 KJ/mol, respectively. These compounds are proposed to be promising pioneer hits.
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spelling doaj.art-9eb36627917b4de6b208215069d517962023-11-22T05:22:32ZengMDPI AGApplied Sciences2076-34172021-07-011115697710.3390/app11156977Identification of Novel Inhibitors of Type-I Mycobacterium Tuberculosis Fatty Acid Synthase Using Docking-Based Virtual Screening and Molecular Dynamics SimulationNidhi Singh0Shi-Qing Mao1Wenjin Li2Institute for Advanced Study, Shenzhen University, Shenzhen 518060, ChinaInstitute for Advanced Study, Shenzhen University, Shenzhen 518060, ChinaInstitute for Advanced Study, Shenzhen University, Shenzhen 518060, ChinaMycobacterial fatty acid synthase type-I (FAS-I) has an important role in the de novo synthesis of fatty acids, which constitute a major component of the cell wall. The essentiality of FAS-I in the survival and growth of mycobacterium makes it an attractive drug target. However, targeted inhibitors against Mycobacterial FAS-I have not been reported yet. Recently, the structure of FAS-I from Mycobacterium tuberculosis was solved. Therefore, in a quest to find potential inhibitors against FAS-I, molecular docking-based virtual screening and molecular dynamics simulation were done. Subsequently, molecular dynamic simulations based on binding free energy calculations were done to gain insight into the predicted binding mode of putative hits. The detailed analysis resulted in the selection of four putative inhibitors. For compounds BTB14738, RH00608, SPB02705, and CD01000, binding free energy was calculated as −72.27 ± 12.63, −68.06 ± 11.80, −63.57 ± 12.22, and −51.28 ± 13.74 KJ/mol, respectively. These compounds are proposed to be promising pioneer hits.https://www.mdpi.com/2076-3417/11/15/6977fatty acid synthasemolecular dockingvirtual screeningmolecular dynamics simulationsMM/PBSAbinding free energy
spellingShingle Nidhi Singh
Shi-Qing Mao
Wenjin Li
Identification of Novel Inhibitors of Type-I Mycobacterium Tuberculosis Fatty Acid Synthase Using Docking-Based Virtual Screening and Molecular Dynamics Simulation
Applied Sciences
fatty acid synthase
molecular docking
virtual screening
molecular dynamics simulations
MM/PBSA
binding free energy
title Identification of Novel Inhibitors of Type-I Mycobacterium Tuberculosis Fatty Acid Synthase Using Docking-Based Virtual Screening and Molecular Dynamics Simulation
title_full Identification of Novel Inhibitors of Type-I Mycobacterium Tuberculosis Fatty Acid Synthase Using Docking-Based Virtual Screening and Molecular Dynamics Simulation
title_fullStr Identification of Novel Inhibitors of Type-I Mycobacterium Tuberculosis Fatty Acid Synthase Using Docking-Based Virtual Screening and Molecular Dynamics Simulation
title_full_unstemmed Identification of Novel Inhibitors of Type-I Mycobacterium Tuberculosis Fatty Acid Synthase Using Docking-Based Virtual Screening and Molecular Dynamics Simulation
title_short Identification of Novel Inhibitors of Type-I Mycobacterium Tuberculosis Fatty Acid Synthase Using Docking-Based Virtual Screening and Molecular Dynamics Simulation
title_sort identification of novel inhibitors of type i mycobacterium tuberculosis fatty acid synthase using docking based virtual screening and molecular dynamics simulation
topic fatty acid synthase
molecular docking
virtual screening
molecular dynamics simulations
MM/PBSA
binding free energy
url https://www.mdpi.com/2076-3417/11/15/6977
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AT wenjinli identificationofnovelinhibitorsoftypeimycobacteriumtuberculosisfattyacidsynthaseusingdockingbasedvirtualscreeningandmoleculardynamicssimulation