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Computational screening of dipeptidyl peptidase IV inhibitors from micoroalgal metabolites by pharmacophore modeling and molecular docking
Author(s) -
Selvaraj Gurudeeban,
Kaliamurthi Satyavani,
Cakmak Zeynep E.,
Cakmak Turgay
Publication year - 2016
Publication title -
phycological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.438
H-Index - 44
eISSN - 1440-1835
pISSN - 1322-0829
DOI - 10.1111/pre.12141
Subject(s) - pharmacophore , virtual screening , docking (animal) , autodock , chembl , stereochemistry , biochemistry , chemistry , biology , in silico , drug discovery , medicine , nursing , gene
SUMMARY Dipeptidyl peptidase IV ( DPP‐IV ) catalyzes conversion of GLP‐1 (glucagon like peptide 1) to inert structure, which results in insufficient secretion of insulin and increase in postprandial blood glucose level. The present study attempts to identify novel inhibitors from bioactive metabolites present in microalgae against DPP‐IV through virtual screening, molecular docking, and pharmacophore modeling for the active target. Possible binding modes of all 60 ligands against DPP‐IV receptor were constructed using MT iOpenScreen virtual screening server. Pharmacophore model was built based on identified 38 DPP‐IV test ligands by using the web‐based PharmaGist program which encompasses hydrogen‐bond acceptors, hydrophobic groups, spatial features, and aromatic rings. The pharmacophore model having highest scores was selected to screen active DPP‐IV ligands. Highest scoring model was used as a query in ZincPharmer screening. All identified ligands were filtered, based on the Lipinski's rule‐of‐five and were subjected to docking studies. In the process of docking analyses, we considered different bonding modes of one ligand with multiple active cavities of DPP‐IV with the help of AutoDock 4.0. The docking analyses indicate that the bioactive constituents, namely, β‐stigmasterol, barbamide, docosahexaenoic acid, arachidonic acid, and harman showed the best binding energies on DPP‐IV receptor and hydrogen bonding with ASP545 , GLY741 , TYR754 , TYR666 , ARG 125, TYR 547, SER 630, and LYS 554 residues. This study concludes that docosahexaenoic acid, arachidonic acid, β‐stigmasterol, barbamide, harman, ZINC 58564986, ZINC 56907325, ZINC 69432950, ZINC 69431828, ZINC 73533041, ZINC 84287073, ZINC 69849395, and ZINC 10508406 act as possible DPP‐IV inhibitors.