Diabetes mellitus termed as metabolic disorder is a collection of interlinked diseases and mainly body’s inability to manage glucose level which leads to cardiovascular diseases, renal failure, neurological disorders, and many others. The drugs contemporarily used for diabetes have many inevitable side effects, and many of them have become less responsive to this multifactorial disorder. Momordica charantia commonly known as bitter gourd has many bioactive compounds with antidiabetic properties. The current study was designed to use computational methods to discover the best antidiabetic peptides devised from hypoglycemic polypeptide-P of M. charantia. The binding affinity and interaction patterns of peptides were evaluated against four receptor proteins (i.e., as agonists of insulin receptor and inhibitors of sodium-glucose cotransporter 1, dipeptidyl peptidase-IV, and glucose transporter 2) using molecular docking approach. A total of thirty-seven peptides were docked against these receptors. Out of which, top five peptides against each receptor were shortlisted based on their S-scores and binding affinities. Finally, the eight best ligands (i.e., LIVA, TSEP, EKAI, LKHA, EALF, VAEK, DFGAS, and EPGGGG) were selected as these ligands strictly followed Lipinski’s rule of five and exhibited good ADMET profiling. One peptide EPGGGG showed activity towards insulin and SGLT1 receptor proteins. The top complex for both these targets was subjected to 50 ns of molecular dynamics simulations and MM-GBSA binding energy test that concluded both complexes as highly stable, and the intermolecular interactions were dominated by van der Waals and electrostatic energies. Overall, the selected ligands strongly fulfilled the drug-like evaluation criterion and proved to have good antidiabetic properties.

中文翻译：

---

苦瓜降糖多肽-P抗糖尿病药物的分子对接与模拟研究


糖尿病被称为代谢紊乱，是一系列相互关联的疾病，主要是身体无法控制血糖水平，导致心血管疾病、肾功能衰竭、神经系统疾病等。目前用于治疗糖尿病的药物有许多不可避免的副作用，其中许多药物对这种多因素疾病的反应减弱。苦瓜俗称苦瓜，含有许多具有抗糖尿病特性的生物活性化合物。目前的研究旨在使用计算方法来发现从苦瓜降血糖多肽-P 中设计的最佳抗糖尿病肽。使用分子对接方法评估肽针对四种受体蛋白（即作为胰岛素受体的激动剂和钠-葡萄糖协同转运蛋白1、二肽基肽酶-IV和葡萄糖转运蛋白2的抑制剂）的结合亲和力和相互作用模式。总共有 37 种肽与这些受体对接。其中，针对每种受体的前五种肽根据其 S 分数和结合亲和力入围。最后，选择了八个最好的配体（即LIVA、TSEP、EKAI、LKHA、EALF、VAEK、DFGAS和EPGGGG），因为这些配体严格遵循Lipinski的五法则并表现出良好的ADMET分析。一种肽 EPGGGG 显示出对胰岛素和 SGLT1 受体蛋白的活性。对这两个目标的顶部复合物进行了 50 ns 的分子动力学模拟和 MM-GBSA 结合能测试，得出这两个复合物高度稳定的结论，并且分子间相互作用以范德华和静电能为主。 总体而言，所选配体强烈满足类药评价标准，并被证明具有良好的抗糖尿病特性。