Numerous experimental data on the human peripheral taste system sugges
t the existence of multiple low-affinity and low-specificity receptor
sites which are responsible for the detection and the complete discrim
ination of a very large number of organic molecules. According to this
hypothesis, a given molecule interacts with numerous taste receptors
and vice versa. Statistical analysis of taste intensities estimated by
58 human subjects for various molecules enables the calculation of ta
ste intermolecular distances. For the present modeling study we hypoth
esized that a short taste distance (i.e. taste similarity) between two
distinct molecules indicates that they bind with similar distribution
s of affinities to the taste receptors, and hence display similar bind
ing motifs. In order to find common molecular binding motifs among 14
selected organic tastants, hydrogen-bonding and hydrophobic interactio
n properties were mapped onto their molecular surfaces. The 14 surface
s were then cut in 240 fragments, most of which were made up of 2-4 po
tentially interacting zones. A correspondence index was defined to mea
sure the analogy between two optimally superimposed fragments. The 75
most representative fragments were all matched pairwise. Twelve distin
ct clusters of fragments were isolated from the 2775 calculated compar
isons. These 12 fragment types were used to calculate structural simil
arity distances. We then performed a combinatorial analysis to identif
y which fragment combination best reconciled structural and taste dist
ances. We finally identified an optimal subset of seven fragment types
out of the 12, which significantly and best accounted for the 91 pair
wise taste distances between all 14 modeled tastants. These seven vali
dated fragment types are therefore presented as good candidates to be
recognized by the same number of distinct taste receptor sites. Potent
ial applications of these identified binding motifs to tastant design
are suggested.