Open AccessThe search for dipeptidyl peptidase iv (DPP4) inhibitors for the treatment of type 2 diabetes: an in-silico study
Author(s) -
Ruslin Ruslin,
K Al-Febriana,
Ida Usman,
Muhammad Arba
Publication year - 2021
Publication title -
journal of physics. conference series
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.21
H-Index - 85
eISSN - 1742-6596
pISSN - 1742-6588
DOI - 10.1088/1742-6596/1899/1/012051
Subject(s) - pharmacophore , in silico , chemistry , dipeptidyl peptidase , dipeptidyl peptidase 4 , binding affinities , docking (animal) , ligand (biochemistry) , small molecule , molecule , stereochemistry , binding site , enzyme , hydrogen bond , type 2 diabetes , biochemistry , diabetes mellitus , biology , medicine , endocrinology , receptor , nursing , organic chemistry , gene
Dipeptidyl Peptidase IV (DPP4) enzyme is a dissolved plasma enzyme found in the intestinal, kidney and liver capillaries that degrade the Glucagon Like Peptide-1 (GLP-1), which is crucial in regulating blood glucose levels. Thus, DPP4 inhibition was considered as an important strategy to combat diabetes. In this research, a pharmacophore modeling and molecular docking was conducted to identify the potential hits of DPP4 inhibitors. The pharmacophore features consisted of three hydrogen bonds acceptors and one positive ion with Area Under Curve of Receiver Operating Characteristic (AUC-ROC) were 0.72 and GH score of 0.592. Screening on the ZINC database resulted in 1151 hit molecules, in which all molecules were subjected to molecular docking to explore their binding interactions. The binding energies of all ligand were between -5.08 and -10.56 kcal/mol, in which four hit molecules, i.e. The four best hit molecules in term of binding orientation and binding energy were Lig_1418/zinc215387739, Lig_37/zinc7983247, Lig_1432/zinc100998449, and Lig_1037/zinc104157322, exhibited better affinities than that of cognate ligand (ABT341, E=-9.98 kcal/mol), which indicated their potentials as novel DPP4 inhibitors.