Abstract

Plant derived product can be used as other alternatives to currently used drugs for controlling chronic diseases like Diabetes mellitus. The potential of Coagulin L (a constituent of Withania coagulans) as dipeptidyl peptidase-4 (DPP-4) inhibitor was evaluated by molecular modelling study. It was observed that amino acid residues such as Glu205, Glu206, Tyr 547, His 740, and Try662 interacts with Coagulin L and Saxagliptin (a known DPP-4 inhibitor). Other nonbonded interactions of Coagulin L and Saxagliptin with DPP-4 binding residues were also found similar. The docking energy of Coagulin L was found to be −7.69 Kcal/mol whereas −8.44 kcal/mol was recorded for Saxagliptin. MD simulation study revealed stable binding throughout 100 ns simulation. RMSD plot of the complex was stabilized in 43 ns and remained stable during entire simulation(100 ns). RMSF plot of DPP-4 Coagulin L interaction showed major fluctuations at residue 246 and 766, however, Arg 125, Glu 205, Ser 209 and His 740 showed no major perturbations. Principal Component Analysis showed that important dynamics of the protein remain unchanged during entire simulation since the non-polar, van der waals, ionic interaction and solvation energy, altogether play important role in the complex stability. The molecular modelling study of DPP-4 with Coagulin L was an effort to establish correlation with traditional practices of Withania coagulans as antidiabetic agent in Indian subcontinent.

Communicated by Ramaswamy H. Sarma

摘要

植物衍生产品可用作目前用于控制糖尿病等慢性疾病的药物的其他替代品。Coagulin L（Withania coagulans的一种成分）的潜力) 作为二肽基肽酶 4 (DPP-4) 抑制剂，通过分子模型研究进行了评估。观察到 Glu205、Glu206、Tyr 547、His 740 和 Try662 等氨基酸残基与凝固素 L 和沙格列汀（一种已知的 DPP-4 抑制剂）相互作用。其他与 DPP-4 结合残基的凝固素 L 和沙格列汀的非键相互作用也相似。发现 Coagulin L 的对接能量为 -7.69 Kcal/mol，而 Saxagliptin 记录为 -8.44 kcal/mol。MD 模拟研究揭示了在整个 100 ns 模拟过程中的稳定结合。配合物的 RMSD 图在 43 ns 内稳定，并在整个模拟期间（100 ns）保持稳定。DPP-4 凝固素 L 相互作用的 RMSF 图显示在残基 246 和 766 处有较大波动，然而，Arg 125、Glu 205、Ser 209 和 His 740 没有显示出大的扰动。主成分分析表明，在整个模拟过程中，蛋白质的重要​​动力学保持不变，因为非极性、范德华力、离子相互作用和溶剂化能共同对复合物的稳定性起重要作用。DPP-4 与 Coagulin L 的分子建模研究旨在建立与传统实践的相关性。Withania 凝固素在印度次大陆作为抗糖尿病药物。

由 Ramaswamy H. Sarma 传达