Explicit molecular dynamics simulation studies to discover novel natural compound analogues as Mycobacterium tuberculosis inhibitors
Tuberculosis (TB) in one of the dreadful diseases present globally. This is caused by Mycobacterium tuberculosis. Mycobacterium tuberculosis dethiobiotin synthetase (MtDTBS) is an essential enzyme in biotin biosynthesis and is an ideal target to design and develop novel inhibitors. In order to effec...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023005315 |
| _version_ | 1811161793707376640 |
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| author | Shailima Rampogu Baji Shaik Ju Hyun Kim Tae Sung Jung Min Woo Ha Keun Woo Lee |
| author_facet | Shailima Rampogu Baji Shaik Ju Hyun Kim Tae Sung Jung Min Woo Ha Keun Woo Lee |
| author_sort | Shailima Rampogu |
| collection | DOAJ |
| description | Tuberculosis (TB) in one of the dreadful diseases present globally. This is caused by Mycobacterium tuberculosis. Mycobacterium tuberculosis dethiobiotin synthetase (MtDTBS) is an essential enzyme in biotin biosynthesis and is an ideal target to design and develop novel inhibitors. In order to effectively combat this disease six natural compound (butein) analogues were subjected to molecular docking to determine their binding mode and the binding affinities. The resultant complex structures were subjected to 500 ns simulation run to estimate their binding stabilities using GROMACS. The molecular dynamics simulation studies provided essential evidence that the systems were stable during the progression of 500 ns simulation run. The root mean square deviation (RMSD) of all the systems was found to be below 0.3 nm stating that the systems are well converged. The radius of gyration (Rg) profiles indicated that the systems were highly compact without any major fluctuations. The principle component analysis (PCA) and Gibbs energy landscape studies have revealed that the comp3, comp5 and comp11 systems navigated marginally through the PC2. The intermolecular interactions have further demonstrated that all the compounds have displayed key residue interactions, firmly holding the ligands at the binding pocket. The residue Lys37 was found consistently to interact with all the ligands highlighting its potential role in inhibiting the MtDTBS. Our investigation further put forth two novel compounds (comp10 and comp11) as putative antituberculosis agents. Collectively, we propose six compounds has plausible inhibitors to curtail TB and further can act as scaffolds in designing new compounds. |
| first_indexed | 2024-04-10T06:21:11Z |
| format | Article |
| id | doaj.art-f6023952467f42e2a44b3aa49513ab95 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-10T06:21:11Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-f6023952467f42e2a44b3aa49513ab952023-03-02T05:01:01ZengElsevierHeliyon2405-84402023-02-0192e13324Explicit molecular dynamics simulation studies to discover novel natural compound analogues as Mycobacterium tuberculosis inhibitorsShailima Rampogu0Baji Shaik1Ju Hyun Kim2Tae Sung Jung3Min Woo Ha4Keun Woo Lee5Division of Life Sciences, Division of Applied Life Science (BK21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju, 52828, South Korea; Corresponding author.Department of Chemistry (BK 21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University, Jinju, South KoreaDepartment of Chemistry (BK 21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University, Jinju, South KoreaLaboratory of Aquatic Animal Diseases, Research Institute of Natural Science, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of KoreaJeju Research Institute of Pharmaceutical Sciences, College of Pharmacy, Jeju National University, Jeju, 63243, Republic of Korea; Corresponding author.Division of Life Sciences, Division of Applied Life Science (BK21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju, 52828, South Korea; Corresponding author.;Tuberculosis (TB) in one of the dreadful diseases present globally. This is caused by Mycobacterium tuberculosis. Mycobacterium tuberculosis dethiobiotin synthetase (MtDTBS) is an essential enzyme in biotin biosynthesis and is an ideal target to design and develop novel inhibitors. In order to effectively combat this disease six natural compound (butein) analogues were subjected to molecular docking to determine their binding mode and the binding affinities. The resultant complex structures were subjected to 500 ns simulation run to estimate their binding stabilities using GROMACS. The molecular dynamics simulation studies provided essential evidence that the systems were stable during the progression of 500 ns simulation run. The root mean square deviation (RMSD) of all the systems was found to be below 0.3 nm stating that the systems are well converged. The radius of gyration (Rg) profiles indicated that the systems were highly compact without any major fluctuations. The principle component analysis (PCA) and Gibbs energy landscape studies have revealed that the comp3, comp5 and comp11 systems navigated marginally through the PC2. The intermolecular interactions have further demonstrated that all the compounds have displayed key residue interactions, firmly holding the ligands at the binding pocket. The residue Lys37 was found consistently to interact with all the ligands highlighting its potential role in inhibiting the MtDTBS. Our investigation further put forth two novel compounds (comp10 and comp11) as putative antituberculosis agents. Collectively, we propose six compounds has plausible inhibitors to curtail TB and further can act as scaffolds in designing new compounds.http://www.sciencedirect.com/science/article/pii/S2405844023005315TuberculosisNatural compoundsMolecular dynamics simulationMycobacterium tuberculosis dethiobiotin SynthetaseButein analogues |
| spellingShingle | Shailima Rampogu Baji Shaik Ju Hyun Kim Tae Sung Jung Min Woo Ha Keun Woo Lee Explicit molecular dynamics simulation studies to discover novel natural compound analogues as Mycobacterium tuberculosis inhibitors Heliyon Tuberculosis Natural compounds Molecular dynamics simulation Mycobacterium tuberculosis dethiobiotin Synthetase Butein analogues |
| title | Explicit molecular dynamics simulation studies to discover novel natural compound analogues as Mycobacterium tuberculosis inhibitors |
| title_full | Explicit molecular dynamics simulation studies to discover novel natural compound analogues as Mycobacterium tuberculosis inhibitors |
| title_fullStr | Explicit molecular dynamics simulation studies to discover novel natural compound analogues as Mycobacterium tuberculosis inhibitors |
| title_full_unstemmed | Explicit molecular dynamics simulation studies to discover novel natural compound analogues as Mycobacterium tuberculosis inhibitors |
| title_short | Explicit molecular dynamics simulation studies to discover novel natural compound analogues as Mycobacterium tuberculosis inhibitors |
| title_sort | explicit molecular dynamics simulation studies to discover novel natural compound analogues as mycobacterium tuberculosis inhibitors |
| topic | Tuberculosis Natural compounds Molecular dynamics simulation Mycobacterium tuberculosis dethiobiotin Synthetase Butein analogues |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023005315 |
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