Difference between revisions of "Team:BIT-China/Model/Docking"

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    <h2 class="title-h2">MODEL-Docking </h2>
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<h2 class="title-h2">MODEL-Docking </h2>
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<h3 class="title-h3">STRUCTURE MODEL</h3>
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<h3 class="title-h3">Purpose</h3>
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<h4 class="title-h4">Purpose </h4>
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<p class="my-content-p">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.</p>
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<p class="my-content-p">In order to confirm whether this "radar" T1R2/T1R3 can "sense" the sweetness of different sweetener, we simulated the model of receptor's structure[1] [4]. It was helpful to observe how the sweeteners binding to T1R2/T1R3 receptor visually. Moreover, we expected to find some unknown sweeteners binding sites based on this model, even some ideal sweeteners are still unknown. </p>
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<h4 class="title-h4">Methods</h4>
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<p class="my-content-p">To make the signal input more accurate and reliable, we simulated the T1R2/T1R3 receptor's structure model through SWISS-MODEL. Meanwhile, according to Chemdraw 2D and Chemdraw 3D, we constructed some sweetners' model. And the docking process was performed by using Autodock Vina.</p>
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<h4 class="title-h4">Results</h4>
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<p class="my-content-p">We used homology modeling to obtain the structure of human sweet receptor T1R2/T1R3. According to the crystal protein structure of similar receptor in mice, we only simulated ligand-binding-domain of our receptor. </p>
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<h3 class="title-h3">Method</h3>
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<p class="my-content-p">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.</p>
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              <span>Fig. 3 The simulated structure of human sweetness receptors' ligand-binding domain (LBD)</span>
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<p class="my-content-p">Then, taking advantage of software Chemdraw 2D and Chemdraw 3D, we established some natural or artificial sweeteners' structure.</p>
 
  
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<img class="formula50" src="https://static.igem.org/mediawiki/2017/5/50/T--BIT-China--2017modeling_pic4.png" />
 
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<span>Fig. 4 Three dimensional structure of some sweeteners</span>
 
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<p class="my-content-p">Docking process was carried out under Autodock Vina (Fig. 5-7).</p>
 
  
  
  
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<h3 class="title-h3">Result</h3>
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<p class="my-content-p">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. </p>
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<img src="https://static.igem.org/mediawiki/2017/e/e4/BIT-China_model-docking_fig1.png " />
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<img src="https://static.igem.org/mediawiki/2017/e/e6/BIT-China_model-docking_fig2.png " />
 
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<span>Fig. 5． Docking result of different sweeteners </span>
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<span class="my-pic-span">The structure of T1R2-T1R3(ligand-binding domain) we simulated</span>
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<span>Fig. 6． Docking result of aspartame </span>
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<span class="my-pic-span">Glycyrrhizic acid docks with T1R2-T1R3 receptor structure model</span>
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<span>Fig. 7． Docking result of stevioside </span>
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<img src="https://static.igem.org/mediawiki/2017/5/5f/BIT-China_model-docking_fig3.png  " />
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<span class="my-pic-span">Aspartame docks with T1R2-T1R3 receptor structure model</span>
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<span class="my-pic-span">Stevioside docks with T1R2-T1R3 receptor structure model</span>
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<h3 class="title-h3">Discussion</h3>
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<p class="my-content-p">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.</p>
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<p class="my-content-p">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.</p>
  
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<p class="my-content-p">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.</p>
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<h4 class="title-h4">Discussion</h4>
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<p class="my-content-p">According to the results, all common, representative sweet substances can bind to human T1R2/T1R3 receptors on ligand-binding Domain (LBD). That means there are a lot of sites in receptor can provide advantage of suitable binding. Although model is only a part of the whole receptor, this domain is the most important domain for binding. It proves that this receptor can "taste" the sweetness and our project has enormous potential to be used in a wide range of sweet material testing compared to E-Tong.</p>
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<p class="my-content-p">Our docking results estimated that ligand-binding domain (LBD) of human T1R2/T1R3 receptors could bind with almost all kinds of known sweeteners. It provided evidence that this receptor has an ability to "taste" the sweetness. Meanwhile, our results also helped us to speculate that the number of both binding-site and binding-molecule also might influence the sense of sweetness.</p>
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<p class="my-content-p">However, our model still needs optimization. We plan to enhance the docking model and the more professional direct would be supplied by it.</p>
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<p class="my-content-p">At the same time, we also find the situation of different sweeteners combination is different, for example the binding number, binding concentration and so on, which demonstrates people for the perception of sweet substances not only depends on the sweetness of the sweetener, but also on the concentration and the number of binding. In the future, it can provide the guidance for us to develop sweetness standards.</p>
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<p class="my-content-p">But our model needs to be improved, in the future, we will use molecular dynamics modeling (molecular docking) and other methods to modify the sweet receptor model utilizing software Gauss View through the Gaussian force field and other mechanical system. The appropriate deformation of the small molecular material is also going to be simulated for making docking results be closer to the real situation.</p>
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Revision as of 14:09, 27 October 2017

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.

TOP

Contact

Institute of Biotransformation and synthetic biosystem

School of life science

Beijing Institute of Technology

100081, Beijing

Email: lichun@bit.edu.cn