A two-stage computational approach to predict novel ligands for a chemosensory receptor

Amara Jabeen, Ramya Vijayram, Shoba Ranganathan*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)
    72 Downloads (Pure)


    Olfactory receptor (OR) 1A2 is the member of largest superfamily of G protein-coupled receptors (GPCRs). OR1A2 is an ectopically expressed receptor with only 13 known ligands, implicated in reducing hepatocellular carcinoma progression, with enormous therapeutic potential. We have developed a two-stage screening approach to identify novel putative ligands of OR1A2. We first used a pharmacophore model based on atomic property field (APF) to virtually screen a library of 5942 human metabolites. We then carried out structure-based virtual screening (SBVS) for predicting the potential agonists, based on a 3D homology model of OR1A2. This model was developed using a biophysical approach for template selection, based on multiple parameters including hydrophobicity correspondence, applied to the complete set of available GPCR structures to pick the most appropriate template. Finally, the membrane-embedded 3D model was refined by molecular dynamics (MD) simulations in both the apo and holo forms. The refined model in the apo form was selected for SBVS. Four novel small molecules were identified as strong binders to this olfactory receptor on the basis of computed binding energies.
    Original languageEnglish
    Pages (from-to)213-221
    Number of pages9
    JournalCurrent Research in Structural Biology
    Publication statusPublished - 2020

    Bibliographical note

    Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


    • Olfactory receptor
    • OR1A2
    • Molecular dynamics
    • Atomic property field
    • Virtual ligand screening
    • Binding free energy calculation
    • Hydrophobicity correspondence


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