Molecular Docking and Simulation Studies of Antidiabetic Agents Devised from Hypoglycemic Polypeptide-P of Momordica charantia

Abstract

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.

Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity

“…In addition to the presence of natural compounds, Momordica charantia can synthesize peptides that can bind to the insulin receptor, lowering blood glucose levels. These peptides may help reduce the need for insulin and limit the side effects of antidiabetic drugs [ 59 ].…”

“…The hypoglycaemic activity of insulin-like peptides from Momordica charantia was determined using a molecular docking approach. The study investigated the activity of several peptides such as LIVA, EKAI, EALF, DFGAS and EPGGGG on four target proteins, namely the experimentally determined structures of IR, SGLT1, dipeptidyl peptidase-IV, and the predicted 3D structure of GLUT2 ( Table 1 ) [ 59 ]. In the Sadiq et al study, bioactive components in Eryngium caeruleum were discovered using GC-MS and HPLC-DAD investigations.…”

“…Arif et al [ 59 ] also evaluated the complex binding energies of peptides to selected targets by applying the molecular mechanics generalized born surface area (MM-GBSA) method on 50 ns trajectories obtained by MD simulations of LIVA-IR and DFGAS-SGLT1 complexes. MD simulations revealed the stability of complexes, and calculated binding energies showed significantly favourable interactions between ligands and targets.…”

“…MD simulations revealed the stability of complexes, and calculated binding energies showed significantly favourable interactions between ligands and targets. The ligands appear to be stabilized at the binding sites by van der Waals energy, the nonpolar energy term being the most important for complex formation [ 59 ].…”

A Comprehensive Computational Screening of Phytochemicals Derived from Saudi Medicinal Plants against Human CC Chemokine Receptor 7 to Identify Potential Anti-Cancer Therapeutics

“…The crystal structure of CCR7 is available in the protein data bank [14] and could serve as an excellent starting receptor to be used in computational drug design methods. In advanced drug development strategies, structural-based drug design is an effective way to accelerate lead molecule identification [15][16][17]. Considering this, in this study, we performed structurebased virtual screening of phytochemicals collected from Saudi medicinal plants [18].…”