Abstract
The umami taste receptor is a heterodimer composed of two members of the T1R taste receptor family: T1R1 (taste receptor type 1 member 1) and T1R3 (taste receptor type 1 member 3). Taste receptor T1R1-T1R3 can be activated, or modulated, by binding to several natural ligands, such as L-glutamate, inosine-5’-monophosphate (IMP), and guanosine-5’-monophosphate (GMP). Because no structure of the umami taste receptor has been solved until now, in silico techniques, such as homology modelling, molecular docking, and molecular dynamics (MD) simulations, are used to generate a 3D structure model of this receptor and to understand its molecular mechanisms. The purpose of this chapter is to highlight how computational methods can provide a better deciphering of the mechanisms of action of umami ligands in activating the umami taste receptors leading to advancements in the taste research field.
Keywords
- Homology modelling
- In silico techniques
- Inosine-5′-monophosphate
- l-glutamate
- Molecular dynamics
- Umami taste receptor
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Notes
- 1.
Root-mean-square-deviation (RMSD): standard measure of structural distance between coordinates. It measures the average distance between a group of atoms. The RMSD of certain atoms in a molecule with respect to a reference structure, rref, is calculated as
$$ \mathrm{RMSD}(t)={\left[\frac{1}{M}\sum \limits_{i=1}^N{m}_i{\left|{r}_i(t)-{r_i}^{\mathrm{ref}}\right|}^2\right]}^{\frac{1}{2}} $$where \( M=\sum \limits_{i=1}^N{m}_i \) and ri (t) is the position of atom i at time t after least square fitting the structure to the reference structure.
- 2.
Root-mean-square-fluctuation (RMSF): average deviation of a particle over time from a reference position. It analyzes the portions of the structure that are fluctuating from their mean structure. The RMSF is a measure of the deviation between the position of particle i and some reference position:
$$ {\mathrm{RMSF}}_i={\left[\frac{1}{T}\sum \limits_{t_j=1}^T{\left|{r}_i\left({t}_j\right)-{r_i}^{\mathrm{ref}}\right|}^2\right]}^{\frac{1}{2}} $$where T is the time over which one wants to average and riref is the reference position of particle i.
- 3.
HINT is a scoring function developed by Donald Abraham and Glen Kellogg of the University of Virginia in 1991 with the collaboration of Pietro Cozzini and Andrea Mozzarelli. HINT (Hydropathic INTeraction) is a force field that allows to estimate the variation of the Gibbs free energy (ΔG0), expressed in kcal/mol or kJ/mol, which is generated in the formation of the protein-ligand complex, starting from the calculation of the logPo/w.
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Acknowledgments
The molecular dynamics simulations were performed thanks to Iscra-C grant of 50000 computers hours on High Performance Computing system, CINECA, Bologna, Italy.
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Spaggiari, G., Cavaliere, F., Cozzini, P. (2021). The Application of In Silico Methods on Umami Taste Receptor. In: Palmer, R.K., Servant, G. (eds) The Pharmacology of Taste . Handbook of Experimental Pharmacology, vol 275. Springer, Cham. https://doi.org/10.1007/164_2021_515
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