Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh, Assam, India.
Pediatric Research Institute, Children's Hospital Affiliated to Shandong University, Jinan, China.
J Biomol Struct Dyn. 2023;41(22):12808-12824. doi: 10.1080/07391102.2023.2175378. Epub 2023 Feb 8.
Knipholone is an antiplasmodial phytocompound obtained from the roots of . Despite several available studies, the molecular drug targets of knipholone in remained unknown. Nowadays, techniques are widely used to study the molecular interactions between compounds and proteins as they provide results quickly with high precision and accuracy. In this study, we aim to identify the potential molecular drug targets of knipholone in . We selected 10 proteins of with unique metabolic functions and we found that knipholone showed better binding affinity than the native ligands of 6 proteins. Out of the 6 proteins, knipholone showed better enzyme inhibitory potential than the native ligands of 4 proteins. We carried out a 100 ns MD simulations for knipholone and the native ligands of four proteins and this was followed by binding free energy calculations. In each step, the performance of knipholone was compared to the native ligands of the proteins. Knipholone outperformed the native ligand of Glutathione-S-Transferase (1OKT) at crucial computational studies as evidence from the lower protein-ligand root mean square deviation value, protein root mean square fluctuation value, and protein-ligand binding free energies. The ligand properties of knipholone provide additional evidence for its stability and it maintains adequate protein-ligand contacts during the entire simulation. The density functional theory study also supported the stability of knipholone at the active binding site of 1OKT. From the studied proteins, we conclude that Glutathione-S-Transferase is the most favorable drug target for knipholone in .Communicated by Ramaswamy H. Sarma.
紫檀芪酮是一种抗疟植物化合物，从 的根部分离得到。尽管有几项现有研究，但紫檀芪酮在 中的分子药物靶点仍然未知。如今，技术被广泛用于研究化合物和蛋白质之间的分子相互作用，因为它们能够快速提供高精度和准确性的结果。在这项研究中，我们旨在确定紫檀芪酮在 中的潜在分子药物靶点。我们选择了 10 种具有独特代谢功能的 蛋白，发现紫檀芪酮与 6 种蛋白的天然配体相比表现出更好的结合亲和力。在这 6 种蛋白中，紫檀芪酮对 4 种蛋白的天然配体表现出更好的酶抑制潜力。我们对紫檀芪酮和 4 种蛋白的天然配体进行了 100ns 的 MD 模拟，随后进行了结合自由能计算。在每个步骤中，都将紫檀芪酮的性能与蛋白的天然配体进行了比较。在关键的计算研究中，紫檀芪酮的表现优于谷胱甘肽-S-转移酶（1OKT）的天然配体，证据是较低的蛋白-配体均方根偏差值、蛋白均方根波动值和蛋白-配体结合自由能。紫檀芪酮的配体性质为其稳定性提供了额外的证据，并且在整个模拟过程中保持了足够的蛋白-配体接触。密度泛函理论研究也支持了紫檀芪酮在 1OKT 活性结合位点的稳定性。在所研究的蛋白中，我们得出结论，谷胱甘肽-S-转移酶是紫檀芪酮在 中最有前途的药物靶点。由 Ramaswamy H. Sarma 传达。
