In-silico Structure Modeling and Docking Studies Using Dipeptidyl Peptidase 4 (DPP4) Inhibitors against Diabetes Type-2

Recently recognized class of oral hypoglycemic, dipeptidyl peptidase (DPP4) inhibitors could block the dipeptidyl peptidase 4 (DPP4) enzymes. DPP4 is an intrinsic membrane glycoprotein and a serine exopeptidase that plays a major role in glucose metabolism and responsible for the degradation of incretins such as GLP-1, therefore providing a useful treatment to diabetes mellitus type 2. The present work focused on the study of the structural homology modeling of dipeptidyl peptidase 4 [Homo sapiens] (NP_001926). The Ramachandran plot of DPP4 (NP_001926.2) has 88.9% residues in the most favoured region while template 2QT9 has 96.1% residues in the most favoured region. The model was validated by using protein structure tools RAMPAGE and Prochek for reliability. Docking studies were further performed to analyze the interaction mode between selected DPP4 inhibitor anagliptin derivative SKK and receptor DPP4 by using Hex 8.0.0. The in-silico analysis was useful to identify the novel inhibitor that illustrates better activity than the other reported inhibitors.