Structure based virtual screening of natural compounds and molecular dynamics simulation: Butirosin as Dipeptidyl peptidase (DPP-IV) inhibitor

Abstract

Type II diabetes mellitus (T2DM) is a major metabolic disorder resulting in increase in morbidity and mortality rates. Dipeptidyl peptidase-IV (DPP-IV) is a validated and interesting target to develop novel and effective antihyperglycemic agents. Herein, we performed virtual screening of Prestwick library of natural compounds using structure based hierarchical methods to screen the potent compounds. Further, evaluations of dock score along with protein ligand interactions studies were performed. The topmost ranked compound was processed for molecular dynamic simulations (MD simulation) studies for 20 ns. In addition, in silico ADME analysis for the selection of compounds having admissible pharmacokinetic properties has been studied. The results of molecular docking suggest that compound Butirosin showed maximum dock score and binding energy as compared to the standard Alogliptin. MD simulation of DPP-IV-Alogliptin and DPP-IV-Butirosin complexes showed good stability throughout the simulation and RMSD values were 2.25 Å and 2.6 Å respectively. Thus, Butirosin could be the potential drug candidate for DPP-IV inhibition. • Dipeptidyl-peptidase-4 is a promising target for TypeII Diabetes Mellitus. • Computational screening of natural hit(s) for inhibition of DPP-4 enzyme. • Pharmacokinetic parameters for the best hits were obtained by in silico ADME. • Molecular dynamic studies indicate the stability of protein ligand complexes.