Pharmacophore-based virtual screening of bioactive peptides as dipeptidyl peptidase 4 inhibitor for type 2 diabetes mellitus drug candidates

Abstract

Background: Diabetes is a chronic disease characterised by high blood sugar levels. Glucose that accumulates in the blood without being properly absorbed by the body's cells can cause various organ problems. If diabetes is not properly controlled, various complications can occur that endanger the life of the affected person. Objective: To find bioactive peptides that have the potential to inhibit di-peptidyl peptidase 4 (DPP-4) enzyme as anti-diabetes drug candidates. Method: This research was carried out using pharmacophore-based virtual screening. Result: The validation of the pharmacophore-based virtual screening method showed that model III, which had five pharmacophore features consisting of three Pi interactions, one hydrogen bond donor, and three hydrogen acceptors, was the best pharmacophore model with the values of AUC 0.59; EF 1.2; Se 0.69; Sp 0.94; ACC 0.84; Ya 0.06; and GH 0.2. The screening of the 168,400 short-chain peptides using validated pharmacophore model III gave 51 tetrapeptides as the hits compounds with a pharmacophore fit score of more than 50.0%. Conclusion: In total, 51 tetrapeptides were enlisted as potential as anti-diabetes mellitus drug candidates.