Identification of potential Gly/NMDA receptor antagonists by cheminformatics approach: a combination of pharmacophore modelling, virtual screening and molecular docking studies

SAR and QSAR in Environmental Research
V G Ugale, Sanjay Bari

Abstract

The Gly/NMDA receptor has become known as potential target for the management of neurodegenerative diseases. Discovery of Gly/NMDA antagonists has thus attracted much attention in recent years. In the present research, a cheminformatics approach has been used to determine structural requirements for Gly/NMDA antagonism and to identify potential antagonists. Here, 37 quinoxaline derivatives were selected to develop a significant pharmacophore model with good certainty. The selected model was validated by leave-one-out cross-validation, an external test set, decoy set and Y-randomization test. Applicability domain was verified by the standardization approach. The validated 3D-QSAR model was used to screen virtual hits from the ZINC database by pharmacophore mapping. Molecular docking was used for assessment of receptor-ligand binding modes and binding affinities. The GlideScore and molecular interactions with critical amino acids were considered as crucial features to identify final hits. Furthermore, hits were analysed for in silico pharmacokinetic parameters and Lipinski's rule of five, demonstrating their potential as drug-like candidates. The PubChem and SciFinder search tools were used to authenticate the novelty of leads re...Continue Reading

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Software Mentioned

QikProp
SciFinder
Ligprep
HTVS
PHASE
GlideScore
Glide SP
Glide SP XP
PubChem

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