Rampogu Shailima, Shaik Baji, Kim Ju Hyun, Jung Tae Sung, Ha Min Woo, Lee Keun Woo
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.
Department of Chemistry (BK 21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University, Jinju, South Korea.
Heliyon. 2023 Jan 30;9(2):e13324. doi: 10.1016/j.heliyon.2023.e13324. eCollection 2023 Feb.
Tuberculosis (TB) in one of the dreadful diseases present globally. This is caused by . dethiobiotin synthetase (DTBS) 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 DTBS. 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.
结核病（TB）是全球存在的可怕疾病之一。这是由……引起的。脱硫生物素合成酶（DTBS）是生物素生物合成中的一种必需酶，是设计和开发新型抑制剂的理想靶点。为了有效对抗这种疾病，对六种天然化合物（紫铆因）类似物进行了分子对接，以确定它们的结合模式和结合亲和力。使用GROMACS对所得的复合物结构进行500纳秒的模拟运行，以估计它们的结合稳定性。分子动力学模拟研究提供了重要证据，表明在500纳秒的模拟运行过程中系统是稳定的。发现所有系统的均方根偏差（RMSD）低于0.3纳米，表明系统收敛良好。回转半径（Rg）曲线表明系统高度紧凑，没有任何重大波动。主成分分析（PCA）和吉布斯自由能景观研究表明，comp3、comp5和comp11系统在PC2上有轻微的移动。分子间相互作用进一步表明，所有化合物都显示出关键残基相互作用，将配体牢固地保持在结合口袋中。发现赖氨酸37残基始终与所有配体相互作用，突出了其在抑制DTBS中的潜在作用。我们的研究进一步提出了两种新型化合物（comp10和comp11）作为推定的抗结核药物。总体而言，我们提出六种化合物是减少结核病的合理抑制剂，并且进一步可以作为设计新化合物的支架。
