Faculty of Science & Environment, Mahatma Gandhi Chitrakoot Gramodaya Vishwavidyalaya, Chitrakoot, India.
Computational Chemistry and Drug Discovery Division, Quanta Calculus, Greater Noida, India.
J Biomol Struct Dyn. 2024 Jan-Feb;42(2):1031-1046. doi: 10.1080/07391102.2023.2243336. Epub 2023 Aug 6.
Type 2 Diabetes (T2D), a chronic metabolic disorder characterized by persistent hyperglycemia, accounts for ∼90% of all types of diabetes. Pancreatic α-amylase is a potential drug target for preventing postprandial hyperglycemia and inhibiting T2D in humans. Although many synthetic drugs have been identified against pancreatic α-amylase, however, reported several side effects, and plant-derived natural products are less explored against T2D. This study tested 34 flavonoids derived from the plant against the human pancreatic α-amylase (HPA) using computational approaches such as molecular docking and molecular dynamics simulation approaches. Schrödinger, a drug discovery package with modules applicable for molecular docking, protein-ligand interaction analysis, molecular dynamics, post-dynamics simulation, and binding free energy calculation, was employed for all computational studies. Four flavonoids, namely, Chlorogenic acid, Withaperuvin F, Withaperuvin H, and Rutin, were picked based on their docking score ranging between -7.03 kcal/mol and -11.35 kcal/mol compared to the docking score -7.3 kcal/mol of reference ligand, i.e. Myricetin. The molecular dynamics analysis suggested that all flavonoids showed considerable stability within the protein's catalytic pocket, except chlorogenic acid, which showed high deviation during the last 15 ns. However, the interactions observed in initial docking and extracted from the simulation trajectory involved > 90% identical residues, indicating the affinity and stability of the docked flavonoids with the protein. Therefore, all four compounds identified in this study are proposed as promising antidiabetic candidates and should be further considered for their and validation.Communicated by Ramaswamy H. Sarma.
2 型糖尿病（T2D）是一种以持续性高血糖为特征的慢性代谢性疾病，占所有糖尿病类型的 90%左右。胰α-淀粉酶是预防餐后高血糖和抑制人类 T2D 的潜在药物靶点。尽管已经鉴定出许多针对胰α-淀粉酶的合成药物，但报告了一些副作用，而植物来源的天然产物在 T2D 方面的研究较少。本研究使用计算方法，如分子对接和分子动力学模拟方法，对 34 种源自植物的类黄酮进行了测试，以评估其对人胰腺α-淀粉酶（HPA）的抑制作用。Schrödinger 是一个药物发现软件包，具有适用于分子对接、蛋白-配体相互作用分析、分子动力学、后动力学模拟和结合自由能计算的模块，用于所有计算研究。根据与参考配体即杨梅素的 docking 得分相比， docking 得分在-7.03 kcal/mol 到-11.35 kcal/mol 之间的四种类黄酮，即绿原酸、withaperuvin F、withaperuvin H 和芦丁，被选中。分子动力学分析表明，除了绿原酸外，所有类黄酮在蛋白的催化口袋中都表现出相当的稳定性，绿原酸在最后 15 ns 表现出高偏差。然而，在初始对接中观察到的相互作用并从模拟轨迹中提取的相互作用涉及>90%相同的残基，表明与蛋白结合的 docked 类黄酮的亲和力和稳定性。因此，本研究中鉴定的所有四种化合物都被提议为有前途的抗糖尿病候选物，应该进一步考虑其活性和验证。由 Ramaswamy H. Sarma 通讯。
