In Silico Molecular Docking and Dynamic Investigations of Bioactive Phytoconstituents from Fenugreek Seeds as a Potent Drug against DPP-IV Enzyme

Abstract

Type 2 diabetes is a metabolic disorder resulting from impaired insulin action or dysfunction in β cells. The incretin hormone, glucagon-like peptide-1, is secreted during the meal intake, and dipeptidyl peptidase IV (DPP-IV) rapidly degrades it. The discovery of new DPP-IV inhibitors from natural resources has become an attractive approach to drug discovery. The aim of this in silico study was to identify potential therapeutic lead compounds from fenugreek (Trigonella foenum-graecum) seeds. Our molecular docking study revealed that 20 compounds out of 46 reported compounds of fenugreek seeds demonstrated high affinities (−8.8 to −4.4 kcal/mol). Further molecular dynamics (MD) simulations followed by principal component analysis showed that isovitexin and deoxyrhapontin stabilized the protein quite well and manifested stable RMSD, RMSF, Rg, and SASA profiles throughout the MD simulations. The Molecular Mechanics-Poisson−Boltzmann surface area (MMPBSA) binding free energy analysis further clarified the higher binding affinity of isovitexin compared to the control.