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

Type2 diabetes is a metabolic disorder resulting from impairedinsulin action or dysfunction in & beta; cells. The incretin hormone,glucagon-like peptide-1, is secreted during the meal intake, and dipeptidylpeptidase IV (DPP-IV) rapidly degrades it. The discovery of new DPP-IVinhibitors from natural resources has become an attractive approachto drug discovery. The aim of this in silico studywas to identify potential therapeutic lead compounds from fenugreek(Trigonella foenum-graecum) seeds. Our moleculardocking study revealed that 20 compounds out of 46 reported compoundsof fenugreek seeds demonstrated high affinities (-8.8 to -4.4kcal/mol). Further molecular dynamics (MD) simulations followed byprincipal component analysis showed that isovitexin and deoxyrhapontinstabilized the protein quite well and manifested stable RMSD, RMSF,Rg, and SASA profiles throughout the MD simulations. The MolecularMechanics-Poisson-Boltzmann surface area (MMPBSA) binding freeenergy analysis further clarified the higher binding affinity of isovitexincompared to the control.