Construction of a quantitative three-dimensional model for odor quality using comparative molecular field analysis...

A quantitative structure-activity relationship (QSAR) study of odorants was performed taking an odor as an activity. As an example, we took the 'green odor of pyrazine derivations' as an activity. Conformational analysis of the pyrazine derivatives was performed, and conformers were selected using the longest side-length of a circumscribed box (LLCB) as a criterion. Comparative molecular field analysis (CoMFA) was used to elucidate the three-dimensional (3D) structural features of the derivatives. As a result, it was found that the steric and electrostatic features of the derivations were correlated with human olfactory detection threshold values. We constructed a quantitative 3D model using the graphic views of CoMFA and partial structures of the derivatives. The prediction of human olfactory detection threshold values of other pyrazine derivatives with green odor was possible by using the 3D model. As another example, we took the 'sweet odor of compounds with various structures' as an activity. A quantitative 3D model for sweet odor was constructed in the same manner. Analysing the structural features of odorants by CoMFA and constructing 3D models for several important odor qualities would help to (i) explain or predict human olfactory detection threshold values of interesting odorants, (ii) design new odorants by suggesting the steric and electrostatic requirements, and (iii) elucidate the mechanism of odorant-receptor interaction.