Team:BIT-China/Model/Docking
Purpose
We establish the receptor structure model. It helps us to understand how the sweeteners bind with T1R2-T1R3 receptor. Otherwise we hope to find some unknown sweeteners’ binding sites through this model, and to find unknown sweeteners. In our project, we need to reform Gα， and structure model can give us some advice in lab.
Method
First, we use the method of homology modeling to establish the structure model of T1R2 / T1R3 on swiss-model, and then we find out the PDB file such as glycyrrhizic acid, aspartame, stevioside, sucralose and sucrose by searching the database, and then use Aotodock for molecular docking.
Result
For crystal structure of human being’s T1R2-T1R3 has not been analyzed , so we use homology modeling method to get the structure of T1R2-T1R3 receptor. We get the homology human structure of ligand binding domain based on the protein structure of fish. And this structure is our model base for molecular docking, besides we use softwares, chemdraw 2D and chemdraw 3D, to build PDB files of sweeteners for docking material.
The structure of T1R2-T1R3(ligand-binding domain) we simulated
Glycyrrhizic acid docks with T1R2-T1R3 receptor structure model
Aspartame docks with T1R2-T1R3 receptor structure model
Stevioside docks with T1R2-T1R3 receptor structure model
Discussion
According to the result analysis, all common, representative sweet substances can combine with human sweet receptor T1R2-T1R3. We find most sweeteners bind with receptor on Cysteine-Rich Domain(CRD). It proves that our project has enormous potential to be used in a wide range of sweet material testing. And in the future, it can guide us to discover new sweeteners.
At the same time, the number of different sweet materials’ combination demonstratives that the perception of sweet substances not only depends on the sweetness of the sweeteners, but also the concentration and the number of binding sites. In the future, it can provide the guidance for us to develop sweetness standard.
But our model is not perfect, in the future we will use molecular dynamics modeling (molecular docking) and other means to modify the sweet receptor, and deformat the small molecular material appropriately through the Gaussian force field and other commonly mechanical system and software (Gauss view ) with a view to the docking results closer to the real situation.
