Multiple human taste receptor sites: a molecular modeling approach

Area of Science:

• Sensory Science
• Computational Chemistry
• Molecular Modeling

Background:

• The human taste system involves numerous low-affinity, low-specificity receptors interacting with many organic molecules.
• A molecule's interaction with multiple receptors and vice versa is hypothesized.
• Taste intensity data from human subjects can quantify taste similarity between molecules.

Purpose of the Study:

• To identify common molecular binding motifs among 14 organic tastants.
• To correlate molecular structure with taste perception.
• To propose candidate binding motifs for taste receptor sites.

Main Methods:

• Mapping hydrogen-bonding and hydrophobic interactions onto molecular surfaces of 14 tastants.
• Fragmenting molecular surfaces and analyzing fragment similarities using a correspondence index.
• Clustering fragments and calculating structural similarity distances.
• Performing combinatorial analysis to reconcile structural and taste distances.

Main Results:

• Twelve distinct clusters of molecular fragments were identified.
• An optimal subset of seven fragment types best explained the taste distances between the 14 tastants.
• These seven fragment types represent potential binding motifs for distinct taste receptor sites.

Conclusions:

• Seven validated molecular fragment types are proposed as key determinants of taste similarity.
• These findings offer insights into the molecular basis of taste perception.
• Identified binding motifs have potential applications in designing novel tastants.