Flavonoids as promising anticancer agents: an <i>in silico</i> investigation of ADMET, binding affinity by molecular docking and molecular dynamics simulations
收藏资源简介：
Cancer is one of the most concerning diseases to humankind. Various treatment strategies are being employed for its treatment, out of which use of natural products is an essential one. Flavonoids have proven to be promising anticancer targets since decades. Also, tubulin is a significant biological target for the development of anticancer agents due to its crucial role in mitosis and abundance throughout the body. In the current study, <i>in silico</i> ADMET parameters of 104 flavonoids were examined, followed by molecular docking with the colchicine binding site of Tubulin protein (PDB; Id 4O2B). The best conformation from each flavonoid subcategory with the best docking score (MolDock score) was further subjected to 100 ns of molecular dynamics to investigate the protein-ligand complex’s stability. Different parameters such as RMSD, RMSF, rGy and SASA were calculated for the six flavonoids using molecular dynamic studies. The top most compound from all the six subcategories of flavonoids elicited best behavior in the colchicine binding site of Tubulin protein. This <i>in silico</i> study employing molecular docking and molecular dynamics simulation provides strong evidence for flavonoids to be excellent anti-tubulin agents for the treatment of cancer. Communicated by Ramaswamy H. Sarma
癌症是人类最为关注的疾病之一，目前临床已采用多种治疗策略，其中天然产物疗法是至关重要的一类治疗手段。数十年来，黄酮类化合物 (flavonoids) 已被证实是极具潜力的抗癌作用靶点。此外，微管蛋白 (tubulin) 因其在细胞有丝分裂中的关键作用与全身广泛分布的特性，成为抗癌药物研发的重要生物学靶点。本研究首先对104种黄酮类化合物的计算机模拟 (in silico) ADMET参数进行了评估，随后针对微管蛋白的秋水仙碱结合位点（PDB编号：4O2B）开展分子对接实验。各黄酮类化合物子类中对接得分（MolDock得分）最优的分子构象，进一步被纳入100纳秒的分子动力学模拟体系，以探究蛋白-配体复合物的稳定性。本研究通过分子动力学模拟，对筛选得到的6种黄酮类化合物计算了均方根偏差 (RMSD)、均方根波动 (RMSF)、回转半径 (rGy) 以及溶剂可及表面积 (SASA) 等多项关键表征参数。来自6个黄酮类化合物子类的最优化合物，在微管蛋白的秋水仙碱结合位点中展现出最优的结合特性。本项采用分子对接与分子动力学模拟的计算机模拟 (in silico) 研究，为黄酮类化合物作为优秀的抗微管蛋白抗癌药物用于癌症治疗提供了坚实的理论依据。本文由Ramaswamy H. Sarma转交刊发。
