Filamentous Temperature Sensitive Mutant Z (FtsZ), an important cell division protein in bacteria, has been validated as a potential target for antibiotics development. Citric acid has been found to inhibit the polymerization of Mycobacterium tuberculosis (MTB) FtsZ and several other drugs have been predicted as potential inhibitors through a gene ontology-based drug repurposing approach. An in-depth study on four of the predicted drugs; Fusidic acid (FusA), l-tryptophan, Carbamic acid, and 2-(3-guanidinophenyl)-3-mercaptopropanoic acid, as potential inhibitors of MTB-FtsZ polymerization was conducted using Citric acid as reference compound. The applied in silico methods involve DFT calculations, molecular docking and molecular dynamics simulations. DFT approach was applied to evaluate selectivity and stability properties of the predicted drugs. Calculated parameters including non-linear optical properties, charge distribution and electrostatic potential analyses enabled selectivity prediction of these potential drugs. DFT-based descriptors revealed FusA as the most potent compound, even more reactive than the referenced compound, Citric acid, which is also supported from the molecular docking study. Parameters including MM/PBSA binding free energies, RMSD, RMSF, RoG and hydrogen bond analysis also support FusA as the best potential MTB-FtsZ polymerization inhibitor, that forms a stable complex with the protein and impose greatest level of rigidity to the protein.

中文翻译：

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药物再利用：夫西地酸作为结核分枝杆菌 FtsZ 聚合的潜在抑制剂——来自 DFT 计算、分子对接和分子动力学模拟的见解

丝状温度敏感突变体 Z (FtsZ) 是细菌中一种重要的细胞分裂蛋白，已被验证为抗生素开发的潜在目标。已发现柠檬酸可抑制结核分枝杆菌 (MTB) FtsZ 的聚合，并且通过基于基因本体的药物再利用方法预测了其他几种药物是潜在的抑制剂。对四种预测药物的深入研究；夫西地酸 (FusA)、l-色氨酸、氨基甲酸和 2-(3-胍基苯基)-3-巯基丙酸作为 MTB-FtsZ 聚合的潜在抑制剂使用柠檬酸作为参考化合物进行。应用的计算机方法涉及 DFT 计算、分子对接和分子动力学模拟。应用 DFT 方法评估预测药物的选择性和稳定性。包括非线性光学特性、电荷分布和静电势分析在内的计算参数使这些潜在药物的选择性预测成为可能。基于 DFT 的描述符显示 FusA 是最有效的化合物，甚至比参考化合物柠檬酸更具反应性，分子对接研究也支持这一点。包括 MM/PBSA 结合自由能、RMSD、RMSF、RoG 和氢键分析在内的参数也支持 FusA 作为最有潜力的 MTB-FtsZ 聚合抑制剂，它与蛋白质形成稳定的复合物并对蛋白质施加最大程度的刚性。基于 DFT 的描述符显示 FusA 是最有效的化合物，甚至比参考化合物柠檬酸更具反应性，分子对接研究也支持这一点。包括 MM/PBSA 结合自由能、RMSD、RMSF、RoG 和氢键分析在内的参数也支持 FusA 作为最有潜力的 MTB-FtsZ 聚合抑制剂，它与蛋白质形成稳定的复合物并对蛋白质施加最大程度的刚性。基于 DFT 的描述符显示 FusA 是最有效的化合物，甚至比参考化合物柠檬酸更具反应性，分子对接研究也支持这一点。包括 MM/PBSA 结合自由能、RMSD、RMSF、RoG 和氢键分析在内的参数也支持 FusA 作为最有潜力的 MTB-FtsZ 聚合抑制剂，它与蛋白质形成稳定的复合物并对蛋白质施加最大程度的刚性。