Evidence for a shape-based recognition of odorants in vivo in the human nose from an analysis of the molecular mechanism of lily-of-the-valley odorants detection in the Lilial and Bourgeonal family using the C/Si/Ge/Sn switch strategy

PLoS One. 2017 Aug 1;12(8):e0182147. doi: 10.1371/journal.pone.0182147. eCollection 2017.

Abstract

We performed an analysis of possible mechanisms of ligand recognition in the human nose. The analysis is based on in vivo odor threshold determination and in vitro Ca2+ imaging assays with a C/Si/Ge/Sn switch strategy applied to the compounds Lilial and Bourgeonal, to differentiate between different molecular mechanisms of odorant detection. Our results suggest that odorant detection under threshold conditions is mainly based on the molecular shape, i.e. the van der Waals surface, and electrostatics of the odorants. Furthermore, we show that a single olfactory receptor type is responsible for odor detection of Bourgeonal at the threshold level in humans in vivo. Carrying out a QM analysis of vibrational energies contained in the odorants, there is no evidence for a vibration-based recognition.

MeSH terms

  • Calcium / chemistry
  • Computer Simulation
  • Humans
  • Ligands
  • Nose / physiology*
  • Odorants*
  • Olfactory Receptor Neurons / physiology*
  • Quantitative Structure-Activity Relationship
  • Receptors, Odorant / physiology
  • Regression Analysis
  • Sensory Thresholds
  • Smell*
  • Surface Properties
  • Temperature

Substances

  • Ligands
  • Receptors, Odorant
  • Calcium

Grants and funding

This work was supported by National Natural Science Foundation of China (grant no. 31250110070), http://www.nsfc.gov.cn/publish/portal1/; MERCATOR Research Center Ruhr, http://www.mercur-research.de/en/; and Deutsche Forschungsgemeinschaft (SFB642), http://www.dfg.de/en/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Givaudan Schweiz AG (Fragrance Research) provided support in the form of salaries for P.K. and research materials, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.