Computational and functional analysis of human bitter taste receptors

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2018-05

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Abstract

Mammals perceive five tastes: sweet, umami, salty, sour, and bitter. The focus of this study is related to the sense of taste or gustation. The sense of taste enables an animal to discriminate nourishment from toxins. The sense of taste is mediated by taste receptor cells. These cells are localized and organized within taste buds. Taste receptor cells are primarily found within the oral cavity, typically on the dorsal surface of the tongue, palate, the oropharynx. There are two taste receptor protein families in mammals: T1R and T2R. Taste receptors are members of the G-protein coupled receptor super family (GPCR). Sequence homology assessments of these receptors place them in two categories: the T1R family is classified as class C; whereas, T2Rs are categorized as class A GPCRs. Twenty-Five T2Rs or bitter taste receptors have been identified in humans. Bitter taste receptors are characterized by seven transmembrane domains along with short amino and carboxyl termini-Class A GPCRs. Most of the research carried out thus far has focused on sweet and umami taste receptors. Bitter taste receptor studies have focused on receptors with known ligands that can activate them. The objective of this study is to elucidate the mechanism of the interactions between bitter taste receptors and tastants (or compounds that elicit a response from a bitter taste receptor). We utilized high-throughput and computationally-derived processes have been utilized to build models for a rational set of receptors; subsequently, we docked the experimentally known agonists with each receptor. Two strategies were adopted for docking-targeted and automatic. Theoretically, approximately, nine hundred receptor-ligand interactions in this high throughput endeavor were assessed. Realistically however, five hundred and seventy-nine interactions were feasible and available for further analysis. Automated docking was not only observed to be always energetically favorable, but also a high number of conformations were observed when compared to targeted docking. Specific residues were identified associated with many ligands for a specific receptor. Common residues were observed to be associated with similar functional groups of ligands.

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Keywords

Bitter taste receptors

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