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Computational Approaches for Decoding Select Odorant-Olfactory Receptor Interactions Using Mini-Virtual Screening.

Harini K, Sowdhamini R - PLoS ONE (2015)

Bottom Line: Ligand docking results were applied on homologous pairs (with varying sequence identity) of ORs from human and mouse genomes and ligand binding residues and the ligand profile differed among such related olfactory receptor sequences.This study revealed that homologous sequences with high sequence identity need not bind to the same/ similar ligand with a given affinity.A ligand profile has been obtained for each of the 20 receptors in this analysis which will be useful for expression and mutation studies on these receptors.

View Article: PubMed Central - PubMed

Affiliation: National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore, India.

ABSTRACT
Olfactory receptors (ORs) belong to the class A G-Protein Coupled Receptor superfamily of proteins. Unlike G-Protein Coupled Receptors, ORs exhibit a combinatorial response to odors/ligands. ORs display an affinity towards a range of odor molecules rather than binding to a specific set of ligands and conversely a single odorant molecule may bind to a number of olfactory receptors with varying affinities. The diversity in odor recognition is linked to the highly variable transmembrane domains of these receptors. The purpose of this study is to decode the odor-olfactory receptor interactions using in silico docking studies. In this study, a ligand (odor molecules) dataset of 125 molecules was used to carry out in silico docking using the GLIDE docking tool (SCHRODINGER Inc Pvt LTD). Previous studies, with smaller datasets of ligands, have shown that orthologous olfactory receptors respond to similarly-tuned ligands, but are dramatically different in their efficacy and potency. Ligand docking results were applied on homologous pairs (with varying sequence identity) of ORs from human and mouse genomes and ligand binding residues and the ligand profile differed among such related olfactory receptor sequences. This study revealed that homologous sequences with high sequence identity need not bind to the same/ similar ligand with a given affinity. A ligand profile has been obtained for each of the 20 receptors in this analysis which will be useful for expression and mutation studies on these receptors.

No MeSH data available.


Best binding mode of Helional to OR.This interaction has the highest score in the IFD runs. There are three H-bonds and one salt bridge interaction between the odorant and the residues of the olfactory receptor. The figure is obtained using the “Ligand Interaction Diagram” of the GLIDE software (Schrödinger Release 2013–1:, version 2.6, Schrödinger, LLC, New York, NY, 2013).
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pone.0131077.g012: Best binding mode of Helional to OR.This interaction has the highest score in the IFD runs. There are three H-bonds and one salt bridge interaction between the odorant and the residues of the olfactory receptor. The figure is obtained using the “Ligand Interaction Diagram” of the GLIDE software (Schrödinger Release 2013–1:, version 2.6, Schrödinger, LLC, New York, NY, 2013).

Mentions: Aldehydes of varying carbon length show high response by human olfactory receptors (Table 9) [62]. Helional is the most potent aldehyde when compared to butanal, hexanal, heptanal, octanal, nonanal and decanal. Helional has the highest average docking score (-5.66kcal/mol) for the twenty olfactory receptors under study by IFD. The average score for other aldehydes are as reported in Table 10. The highest score of helional is -12.26kcal/mol and it forms three H-bonds, one salt bridge and one pi-pi interaction (Fig 12), which results in the most stable interaction as compared to other ligands. Invariably, larger ligands would score better than eugenol due to higher extents of hydrophobic interactions.


Computational Approaches for Decoding Select Odorant-Olfactory Receptor Interactions Using Mini-Virtual Screening.

Harini K, Sowdhamini R - PLoS ONE (2015)

Best binding mode of Helional to OR.This interaction has the highest score in the IFD runs. There are three H-bonds and one salt bridge interaction between the odorant and the residues of the olfactory receptor. The figure is obtained using the “Ligand Interaction Diagram” of the GLIDE software (Schrödinger Release 2013–1:, version 2.6, Schrödinger, LLC, New York, NY, 2013).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4519343&req=5

pone.0131077.g012: Best binding mode of Helional to OR.This interaction has the highest score in the IFD runs. There are three H-bonds and one salt bridge interaction between the odorant and the residues of the olfactory receptor. The figure is obtained using the “Ligand Interaction Diagram” of the GLIDE software (Schrödinger Release 2013–1:, version 2.6, Schrödinger, LLC, New York, NY, 2013).
Mentions: Aldehydes of varying carbon length show high response by human olfactory receptors (Table 9) [62]. Helional is the most potent aldehyde when compared to butanal, hexanal, heptanal, octanal, nonanal and decanal. Helional has the highest average docking score (-5.66kcal/mol) for the twenty olfactory receptors under study by IFD. The average score for other aldehydes are as reported in Table 10. The highest score of helional is -12.26kcal/mol and it forms three H-bonds, one salt bridge and one pi-pi interaction (Fig 12), which results in the most stable interaction as compared to other ligands. Invariably, larger ligands would score better than eugenol due to higher extents of hydrophobic interactions.

Bottom Line: Ligand docking results were applied on homologous pairs (with varying sequence identity) of ORs from human and mouse genomes and ligand binding residues and the ligand profile differed among such related olfactory receptor sequences.This study revealed that homologous sequences with high sequence identity need not bind to the same/ similar ligand with a given affinity.A ligand profile has been obtained for each of the 20 receptors in this analysis which will be useful for expression and mutation studies on these receptors.

View Article: PubMed Central - PubMed

Affiliation: National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore, India.

ABSTRACT
Olfactory receptors (ORs) belong to the class A G-Protein Coupled Receptor superfamily of proteins. Unlike G-Protein Coupled Receptors, ORs exhibit a combinatorial response to odors/ligands. ORs display an affinity towards a range of odor molecules rather than binding to a specific set of ligands and conversely a single odorant molecule may bind to a number of olfactory receptors with varying affinities. The diversity in odor recognition is linked to the highly variable transmembrane domains of these receptors. The purpose of this study is to decode the odor-olfactory receptor interactions using in silico docking studies. In this study, a ligand (odor molecules) dataset of 125 molecules was used to carry out in silico docking using the GLIDE docking tool (SCHRODINGER Inc Pvt LTD). Previous studies, with smaller datasets of ligands, have shown that orthologous olfactory receptors respond to similarly-tuned ligands, but are dramatically different in their efficacy and potency. Ligand docking results were applied on homologous pairs (with varying sequence identity) of ORs from human and mouse genomes and ligand binding residues and the ligand profile differed among such related olfactory receptor sequences. This study revealed that homologous sequences with high sequence identity need not bind to the same/ similar ligand with a given affinity. A ligand profile has been obtained for each of the 20 receptors in this analysis which will be useful for expression and mutation studies on these receptors.

No MeSH data available.