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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MDPI AG
2021-07-01
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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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language | English |
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publishDate | 2021-07-01 |
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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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