Dipeptidyl peptidase-IV is the most crucial key enzyme in Type-II diabetes because it is the only enzyme that cleaves the glucose-mediated polypeptides, i.e., GLP-1 and GIP, into a truncated peptide. This truncated peptide leads to the suppression of insulinotropic response, and hence, the secretion of insulin is downregulated. The proposed work will be initiated with different scaffold-based molecular docking studies using FlexX software. Further, the best-scored molecule(s) will be exposed to the molecular dynamic (MD) simulation for 100 ns to understand the stability of the protein-ligand complex. After MD analysis, the molecule will be studied for enzymatic inhibition assay protocol. Using the best IC50 value, enzyme kinetic protocols will be developed to understand the proper binding mechanism, such as competitive, non-competitive, or mixed inhibition.
Rakesh Kumar intends to achieve the following milestones:
- Identification of potential DPP-IV inhibitor using BioSolveIT software.
- Exploration of the potential molecule by molecular dynamic studies to understand the stability of protein-ligand complexes.
- Novel identified molecules will be studied for enzymatic inhibition assay and enzyme kinetic studies.