In Silico Molecular Study of Tryptophan Bitterness.

Antonella Di Pizio,Alessandro Nicoli

doi:10.3390/molecules25204623

Abstract

Tryptophan is an essential amino acid, required for the production of serotonin. It is the most bitter amino acid and its bitterness was found to be mediated by the bitter taste receptor TAS2R4. Di-tryptophan has a different selectivity profile and was found to activate three bitter taste receptors, whereas tri-tryptophan activated five TAS2Rs. In this work, the selectivity/promiscuity profiles of the mono-to-tri-tryptophans were explored using molecular modeling simulations to provide new insights into the molecular recognition of the bitter tryptophan. Tryptophan epitopes were found in all five peptide-sensitive TAS2Rs and the best tryptophan epitope was identified and characterized at the core of the orthosteric binding site of TAS2R4.

Highlights

Tryptophan is one of the nine essential, or indispensable, amino acids
According to the performed docking studies, it fills in the binding site of the three peptide-sensitive bitter taste receptors in a highly complementary manner, as quantified by Glide Standard Precision (SP) score values that were below −8 kcal/mol in all cases (Table 1)
The tryptophan bitter taste was found to be mediated by TAS2R4 [16], but, to the best of our knowledge, the interaction of this relevant amino acid with the cognate bitter taste receptor has not been investigated

Summary

Introduction

Tryptophan (three-letter code: Trp, one-letter code: W) is one of the nine essential, or indispensable, amino acids. It is required for the production of serotonin and has an important role in many fundamental physiological functions such as sleep, mood, cognition, and behavior [1,2,3]. It is a key component in the human diet. Nutritional tryptophan-containing supplements proved to be highly beneficial in malnutrition and undernutrition states, derived often by certain pathological conditions [4]. Due to its role in the serotonin pathway, tryptophan levels are affected in the course of metabolic disorders, and tryptophan supplements are associated with the medical treatment of several diseases such as depression, sleep disorders, cognitive disorders, anxiety, or neurodegenerative diseases [5].

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Conclusion