Difference between revisions of "Team:NUDT CHINA/Modeling"

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<h2> Modeling</h2>
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<h4>Note</h4>
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<p>In order to be considered for the <a href="https://2015.igem.org/Judging/Awards#SpecialPrizes">Best Model award</a>, you must fill out this page.</p>
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<p>Mathematical models and computer simulations provide a great way to describe the function and operation of BioBrick Parts and Devices. Synthetic Biology is an engineering discipline, and part of engineering is simulation and modeling to determine the behavior of your design before you build it. Designing and simulating can be iterated many times in a computer before moving to the lab. This award is for teams who build a model of their system and use it to inform system design or simulate expected behavior in conjunction with experiments in the wetlab.</p>
+
</style>
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<!--DIA_Container-->
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<style type="text/css">
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#NUDT_Dia_Container
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{
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width: auto;
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margin: 0px 100px;
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}
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</style>
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<style type="text/css">
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<style type="text/css">
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padding: 20px 10px;
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width: auto;
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</style>
 +
<!--NUDT_Footer-->
 +
<style type="text/css">
 +
#NUDT_Footer
 +
{
 +
clear: both;
 +
width: auto;
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padding: 30px 0px;
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font-family: 'verdana',sans-serif;
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#NUDT_Footer p{
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font-family: "Trebuchet MS", Helvetica, sans-serif;
 +
color: #000000;
 +
position: relative;
 +
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 +
font-size: 16px;
 +
}
 +
</style>
 +
<!--Common-->
 +
<div id = "myMainContainer">
 +
<div id = "menu">
 +
<img src="https://static.igem.org/mediawiki/2015/9/99/Menu.png"/>
 +
<li><a id = "HOME" href="https://2015.igem.org/Team:NUDT_CHINA"><span>HOME</span></a></li>
 +
<li><a id = "TEAM" href="https://2015.igem.org/Team:NUDT_CHINA/Team"><span>TEAM</span></a></li>
 +
 +
<li><a id = "PROJECT" href = "#"><span>PROJECT</span></a></li>
 +
<li><a id = "Description" href = "https://2015.igem.org/Team:NUDT_CHINA/Description" class = "b"><span>Description</span></a></li>
 +
<li><a id = "Experiments" href = "https://2015.igem.org/Team:NUDT_CHINA/Experiments" class = "b"><span>Experiments &amp; Protocols</span></a></li>
 +
<li><a id = "Results" href="https://2015.igem.org/Team:NUDT_CHINA/Results"  class = "b"><span>Results</span></a></li>
 +
<li><a id = "Design" href="https://2015.igem.org/Team:NUDT_CHINA/Design" class = "b"><span>Design</span></a></li>
 +
 +
<li><a id = "PARTS" href = "#"><span>PARTS</span></a></li>
 +
<li><a id = "Team" href = "https://2015.igem.org/Team:NUDT_CHINA/Parts" class = "b"><span>Team Parts</span></a></li>
 +
<li><a id = "Basic" href = "https://2015.igem.org/Team:NUDT_CHINA/Basic_Part" class = "b"><span>Basic Parts</span></a></li>
 +
<li><a id = "Composite" href="https://2015.igem.org/Team:NUDT_CHINA/Composite_Part"  class = "b"><span>Composite Parts</span></a></li>
  
<p>
+
 
Here are a few examples from previous teams:
+
<li><a id = "NOTEBOOK" href="https://2015.igem.org/Team:NUDT_CHINA/Notebook"><span>NOTEBOOK</span></a></li> 
</p>
+
<li><a id = "ATTRIBUTIONS" href="https://2015.igem.org/Team:NUDT_CHINA/Attributions"><span>ATTRIBUTIONS</span></a></li> 
<ul>
+
<li><a id = "COLLABORATIONS" href="https://2015.igem.org/Team:NUDT_CHINA/Collaborations"><span>COLLABORATIONS</span></a></li>
<li><a href="https://2014.igem.org/Team:ETH_Zurich/modeling/overview">ETH Zurich 2014</a></li>
+
<li><a id = "HUMAN" href="https://2015.igem.org/Team:NUDT_CHINA/Practices"><span>HUMAN PRACTICES</span></a></li> 
<li><a href="https://2014.igem.org/Team:Waterloo/Math_Book">Waterloo 2014</a></li>
+
<li><a id = "SAFETY" href="https://2015.igem.org/Team:NUDT_CHINA/Safety"><span>SAFETY</span></a></li>  
</ul>
+
<li><a id = "MODELING" href="https://2015.igem.org/Team:NUDT_CHINA/Modeling"><span>MODELING</span></a></li
 +
    </div>
 +
    <div id = "logoContainer">
 +
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 +
    </div>
 +
<link href="https://2015.igem.org/Team:NEFU_China/cleariGEM?action=raw&ctype=text/css" rel="stylesheet" /> </head>
 +
</html>
 +
<html>
 +
<!--Main Container-->
 +
<div id = "NUDT_Container" class = "clearStyle">
 +
<!--subCommon-->
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<div>
 +
<img src="https://static.igem.org/mediawiki/2015/0/06/Team_NUDT_CHINA_banner.jpg" style = "width: 100%; height: auto"/>
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</div>
 +
<h1>MODELING</h1>
 +
<table>
 +
<tr>
 +
<p style = "font-size: 12px; text-align: left; padding: 0px 50px 0px 100px;">TIPS1: The left <B style = "color: #d82545">MENU :)</B> links to other NUDT_CHINA website.</p>
 +
<p style = "font-size: 12px; text-align: left; padding: 0px 50px 0px 100px;">TIPS2: The right <B style = "color: #d82545">NAVIGATE :)</B> posites on content in this page. (Valid when <B style = "color: #d82545">UNFOLDED</B>)</p>
 +
<p style = "font-size: 12px; text-align: left; padding: 0px 50px 0px 100px;">TIPS3: Click <B style = "color: #d82545">SUBTITLE</B> to <B style = "color: #d82545">FOLD/UNFOLD</B> related content. </p>
 +
</tr>
 +
<tr><button id = "slideAll" style = "margin: 0px 50px 0px 100px;"> CLICK TO FOLD/UNFOLD ALL</button>
 +
</tr>
 +
</table>
 +
 
 +
<script type="text/javascript">
 +
$(document).ready(function(){
 +
$("#slideAll").click(function(){
 +
$(".BLANK_Container").slideToggle(300);
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</script>
 +
<!--Abstract-->
 +
<h2 id = "pos1">I.Abstract<B style = "color: #d82545">(CLICK)</B></h2>
 +
<div class = "BLANK_Container" id = "slide1">
 +
<p>This model tries to prove theoretically the TALE-based scaffold system can improve the multi-enzyme reaction efficiency. (You can go <a href = "https://2015.igem.org/Team:NUDT_CHINA/Description" style = "color:#d82545; text-decoration:underline;">PROJECT page</a> to see more.) The core idea is to calculate reaction rate parameters using time driven <B>stochastic simulation method</B>, and compare these parameters of the TALE-based scaffold system and the none-scaffold system. Furthermore, the effect of the multi-enzyme sites on scaffold is studied.</p>
 +
 
 +
<p></p>
 +
<script type="text/javascript">
 +
$(document).ready(function(){
 +
$("#pos1").click(function(){
 +
$("#slide1").slideToggle(300);
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</script>
 +
</div>
 +
<!--Introduction-->
 +
<h2 id = "pos2">II.Introduction<B style = "color: #d82545">(CLICK)</B></h2>
 +
<div class = "BLANK_Container" id = "slide2">
 +
<p>The models to study reaction efficiency are based on <B>reaction molecular dynamics</B>. The basic point of reaction molecular dynamics is that REACTION EQUALS COLLISION. <B>Michaelis-Menten</B> equation is universally applied to build reaction molecular dynamics models. However, although the Michaelis-Menten equation is derived from the collision behavior characteristics, it presumes that the reactant is UNIFORMLY dispersed in the reaction space and the COLLISION EQUALS CONCENTRATION. Therefore, the Michaelis-Menten equation is improper to simulate the scaffold “aggregation” effect where the reactant is UNEVEN.</p>
 +
<p>Stochastic simulation can directly calculate the behavior of every reactant molecule, which can simulate scaffold “aggregation” effect. The idea of stochastic simulation is to transform a difficult question to a sampling question. In other words, in this article, the stochastic simulation method is applied to calculate and assess scaffold system and none-scaffold system parameters in the form of probability distributions.</p>
 +
<center>
 +
<Table>
 +
<tr>
 +
<td><img src="https://static.igem.org/mediawiki/2015/e/e3/NUDT_CHINAmodelPNG1.png" style="width: 80%; height:auto"></td>
 +
</tr>
 +
<tr>
 +
<td>
 +
<p style = "font-size: 12px;">Figure 1. The compare between two methodologies.</p>
 +
</td>
 +
</tr>
 +
</Table>
 +
</center>
 +
<p>The stochastic simulation starts from COLLISION while the Michaelis-Menten equation basic on the CONCENTRATION. The transform from COLLISION to CONCENTRATION requires uniform condition.</p>
 +
<p></p>
 +
<script type="text/javascript">
 +
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 +
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 +
</div>
 +
<!--Molecular Behavior & Simplifying Assumptions-->
 +
<h2 id = "pos3">III.Molecular Behavior &amp; Simplifying Assumptions<B style = "color: #d82545">(CLICK)</B></h2>
 +
<div class = "BLANK_Container" id = "slide3">
 +
<p>We simulated multi-enzyme reaction in <i>E.coli</i>. Considering our limited time, equipment and abilities, we adopted the simplifying assumptions below.</p>
 +
<p id = "pos31"></p>
 +
<h3>Object</h3>
 +
<p>The involved objects are <i>E.coli</i>, reactants, scaffold and enzymes (on or off scaffolds). And the enzyme sites are fixed on scaffolds.</p>
 +
<p id = "pos32"></p>
 +
<h3>Geometry</h3>
 +
<p>The simulation is on two dimension. Thus, <i>E.coli</i>, reactants and enzymes are treated as circle, and the scaffolds are treated as lines.</p>
 +
<center>
 +
<Table>
 +
<tr>
 +
<td><img src="https://static.igem.org/mediawiki/2015/3/31/NUDT_CHINAmodelPNG2a.png" style="width: 200px; height:auto"></td>
 +
<td><img src="https://static.igem.org/mediawiki/2015/b/bf/NUDT_CHINAmodelPNG2b.png" style="width: 200px; height:auto"></td>
 +
<td><img src="https://static.igem.org/mediawiki/2015/c/c9/NUDT_CHINAmodelPNG2c.png" style="width: 200px; height:auto"></td>
 +
</tr>
 +
<tr>
 +
<td><p style = "font-size: 12px;">(a) <i>E.coli</i></p></td>
 +
<td><p style = "font-size: 12px;">(b) Simplified <i>E.coli</i> with scaffold</p></td>
 +
<td><p style = "font-size: 12px;">(c) Simplified <i>E.coli</i> without scaffold</p></td>
 +
</tr>
 +
<tr><td colspan=3><p style = "font-size: 12px;">Figure 2. The simplification of <i>E.coli</i></p></td></tr>
 +
</Table>
 +
</center>
 +
<p id = "pos33"></p>
 +
<h3>Motion</h3>
 +
<p>The simulation is time driven. Enzymes and scaffolds are fixed in <i>E.coli</i>. The motion of substrates and intermediate products is the composition of the cyclosis and random thermal motion. We neglected the cyclosis here.</p>
 +
<p>The random thermal motion makes them go forward to an uncertain direction. The motion direction and speed in a time step can decide the random thermal motion, where the direction and speed are uniformly distributed. We abandoned the more accurate Maxwell molecular velocity to improve the calculation speed by voiding probability integral of Maxwell distribution.</p>
 +
<p id = "pos34"></p>
 +
<h3>Interaction</h3>
 +
<p>All object are restricted to move within on <i>E.coli</i>. We neglect the non-contact intermolecular force. The substrates and intermediate products can overlap the enzyme and scaffold spot which can simulate the combination during reaction process.</p>
 +
<center>
 +
<Table>
 +
<tr>
 +
<video width="288px" height="232px" controls="controls">
 +
<source src="https://static.igem.org/mediawiki/2015/c/c2/NUDT_CHINAmodelmp4demo.mp4" type="video/mp4"></source>
 +
Sorry, your browser does not support the video tag. :)
 +
</video>
 +
</tr>
 +
<tr>
 +
<td><p style = "font-size: 12px;">The demo of the reactant motion and interaction (First 30 time units in 3000 time units)</p></td>
 +
</tr>
 +
</Table>
 +
</center>
 +
<p>Every collision (overlap) between reactant and enzyme is effective as long as the they match. And every reaction can be finished instantaneously as long as the collision happened.</p>
 +
<p>The smaller blue dots are substrates and the larger blue and red dots are different enzyme. The different enzymes of (b) are linked by scaffold and the scaffold are independently dispersed while those in (c) are independently dispersed.</p>
 +
<script type="text/javascript">
 +
$(document).ready(function(){
 +
$("#pos3").click(function(){
 +
$("#slide3").slideToggle(300);
 +
});
 +
});
 +
</script>
 +
</div>
 +
<!--Simulation Environment/Platform-->
 +
<h2 id = "pos4">IV.Simulation Environment/Platform<B style = "color: #d82545">(CLICK)</B></h2>
 +
<div class = "BLANK_Container" id = "slide4">
 +
<p>MATLAB &amp; MacBook Pro 2.8 GHz Intel Core i7</p>
 +
<script type="text/javascript">
 +
$(document).ready(function(){
 +
$("#pos4").click(function(){
 +
$("#slide4").slideToggle(300);
 +
});
 +
});
 +
</script>
 +
</div>
 +
<!--Parameters Setting-->
 +
<h2 id = "pos5">V.Parameters Setting<B style = "color: #d82545">(CLICK)</B></h2>
 +
<div class = "BLANK_Container" id = "slide5">
 +
<p>The simulation aims at comparing the scaffold and none-scaffold effect and studying the sites position (on scaffold) effect. The parameters setting below balanced the simulation similarity degree and calculation ability of our equipment. So the reactants, enzyme quantities cell diameter are smaller than the <i>E.coli</i>. But the density of reactants, enzyme is relatively near to the real condition.</p>
 +
<center>
 +
<table>
 +
<tr>
 +
<td style = "padding: 0px 20px; text-align:left;">Simulation Time Step</td>
 +
<td style = "padding: 0px 20px; text-align:left;">1</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px; text-align:left;">Simulation Total Time </td>
 +
<td style = "padding: 0px 20px; text-align:left;">2000</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px; text-align:left;">Reactant speed lower limit (times to reactant diameter)</td>
 +
<td style = "padding: 0px 20px; text-align:left;">0.3</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px; text-align:left;">Reactant speed upper limit (times to reactant diameter)</td>
 +
<td style = "padding: 0px 20px; text-align:left;">2</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px; text-align:left;">Scaffold Quantity</td>
 +
<td style = "padding: 0px 20px; text-align:left;">4</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px; text-align:left;">Initial Reactant Quantity</td>
 +
<td style = "padding: 0px 20px; text-align:left;">150</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px; text-align:left;">Reactant Diameter</td>
 +
<td style = "padding: 0px 20px; text-align:left;">3</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px; text-align:left;">Cell Diameter</td>
 +
<td style = "padding: 0px 20px; text-align:left;">200</td>
 +
</tr>
 +
<tr><td colspan=2><p style = "font-size: 12px;">Table.1 The Constant Parameters Setting</p></td></tr>
 +
</table>
 +
</center>
 +
<center>
 +
<table style = "width:600px; height:auto">
 +
<tr>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td rowspan = 9><img src="https://static.igem.org/mediawiki/2015/f/f3/NUDT_CHINAmodelPNG3.png" style="width: 200px; height:auto"</td>
 +
</tr>
 +
<tr>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
</tr>
 +
<tr>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px;"><p></p></td>
 +
<td style = "padding: 0px 20px;">Enzyme Type</td>
 +
<td style = "padding: 0px 20px;">Enzymes Distance</td>
 +
<td style = "padding: 0px 20px;">Enzymes Diameter</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px;">Group 1</td>
 +
<td style = "padding: 0px 20px;">2</td>
 +
<td style = "padding: 0px 20px;">8</td>
 +
<td style = "padding: 0px 20px;">[6,8]</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px;">Group 2</td>
 +
<td style = "padding: 0px 20px;">2</td>
 +
<td style = "padding: 0px 20px;">16</td>
 +
<td style = "padding: 0px 20px;">[6,8]</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px;">Group 3</td>
 +
<td style = "padding: 0px 20px;">2</td>
 +
<td style = "padding: 0px 20px;">18</td>
 +
<td style = "padding: 0px 20px;">[6,8]</td>
 +
</tr>
 +
<tr>
 +
<td style = "padding: 0px 20px;">Group 4</td>
 +
<td style = "padding: 0px 20px;">3</td>
 +
<td style = "padding: 0px 20px;">[12,12]</td>
 +
<td style = "padding: 0px 20px;">[6,8,10]</td>
 +
</tr>
 +
<tr><td colspan=4><p style = "font-size: 12px;">Table.2 The Variable Parameters Setting</p></td></tr>
 +
<tr>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p></p></td>
 +
<td><p style = "font-size: 12px;">Graphic Note</p></td>
 +
</tr>
 +
</table>
 +
</center>
 +
 
 +
<script type="text/javascript">
 +
$(document).ready(function(){
 +
$("#pos5").click(function(){
 +
$("#slide5").slideToggle(300);
 +
});
 +
});
 +
</script>
 +
</div>
 +
<!--Result-->
 +
<h2 id = "pos6">VI.Result &amp; Analysis<B style = "color: #d82545">(CLICK)</B></h2>
 +
<div class = "BLANK_Container" id = "slide6">
 +
<p>The multi-enzyme reaction series is:</p>
 +
<tr></tr>
 +
<center>
 +
<img src="https://static.igem.org/mediawiki/2015/e/ed/NUDT_CHINAmodelPNG4.png" style="width: 300px; height:auto">
 +
</center>
 +
<p style = "padding: 0px auto"><B style = "color: #d82545">Note1:</B> Return to <a href = "#pos5" style = "color:#d82545; text-decoration:underline;">V.Parameter Setting</a> to see detailed parameter of the group below.</p>
 +
<p style = "padding: 0px auto"><B style = "color: #d82545">Note2:</B> All movies are the first 30 time units in 3000 time units.</p>
 +
 
 +
 
 +
<h3>Group 1</h3>
 +
<center>
 +
<video width="312px" height="132px" controls="controls">
 +
<source src="https://static.igem.org/mediawiki/2015/c/ce/NUDT_CHINAmodelmp4-1.mp4" type="video/mp4"></source>
 +
Sorry, your browser does not support the video tag. :)
 +
</video>
 +
<p></p>
 +
<table style = "padding: 0px 150px">
 +
<td><img src="https://static.igem.org/mediawiki/2015/7/76/NUDT_CHINAmodelPNG5b.png" style="width: 400px; height:auto"></td>
 +
<td style = "padding: 0px 0px; text-align:left;"><p><B style = "color: #d82545">Analysis: </B>Although the substrates are consumed in similar speed. With scaffold the, the intermediate products are transformed to resultant faster than that without scaffold. Thus, the scaffold design improves the reaction efficiency.</p><td>
 +
</table>
 +
</center>
 +
 
 +
<h3>Group 2</h3>
 +
<center>
 +
<video width="312px" height="132px" controls="controls">
 +
<source src="https://static.igem.org/mediawiki/2015/4/4c/NUDT_CHINAmodelmp4-2.mp4" type="video/mp4"></source>
 +
Sorry, your browser does not support the video tag. :)
 +
</video>
 +
<p></p>
 +
<table style = "padding: 0px 150px">
 +
<td><img src="https://static.igem.org/mediawiki/2015/1/17/NUDT_CHINAmodelPNG5a.png" style="width: 400px; height:auto"></td>
 +
<td style = "padding: 0px 0px; text-align:left;"><p><B style = "color: #d82545">Analysis: </B>The distance between enzyme sites is larger than group1. But, similarly, the substrates are consumed in nearly same speed. With scaffold the, the intermediate products are transformed to resultant faster than that without scaffold. Thus, the scaffold design improves the reaction efficiency.</p><td>
 +
</table>
 +
</center>
 +
 
 +
<h3>Group 3</h3>
 +
<center>
 +
<video width="312px" height="132px" controls="controls">
 +
<source src="https://static.igem.org/mediawiki/2015/c/ca/NUDT_CHINAmodelmp4-3.mp4" type="video/mp4"></source>
 +
Sorry, your browser does not support the video tag. :)
 +
</video>
 +
<p></p>
 +
<table style = "padding: 0px 150px">
 +
<td><img src="https://static.igem.org/mediawiki/2015/b/b7/NUDT_CHINAmodelPNG5c.png" style="width: 400px; height:auto"></td>
 +
<td style = "padding: 0px 0px; text-align:left;"><p><B style = "color: #d82545">Analysis: </B>The distance between enzyme sites is enlarged on. Differently, the scaffold design and none-scaffold design have similar reaction efficiency.</p><td>
 +
</table>
 +
</center>
 +
<h3>Group 4</h3>
 +
<center>
 +
<video width="312px" height="132px" controls="controls">
 +
<source src="https://static.igem.org/mediawiki/2015/a/a8/NUDT_CHINAmodelmp4-4.mp4" type="video/mp4"></source>
 +
Sorry, your browser does not support the video tag. :)
 +
</video>
 +
<p></p>
 +
<table style = "padding: 0px 150px">
 +
<td><img src="https://static.igem.org/mediawiki/2015/9/90/NUDT_CHINAmodelPNG5d.png" style="width: 400px; height:auto"></td>
 +
<td style = "padding: 0px 0px; text-align:left;"><p><B style = "color: #d82545">Analysis: </B>The multi-enzyme reaction series increases than that above. The substrates are also consumed in nearly same speed. But the effect of the scaffold is more obvious than that above.</p><td>
 +
</table>
 +
</center>
 +
<h3>Group 1/2/3</h3>
 +
<center>
 +
<Table>
 +
<tr>
 +
<td><img src="https://static.igem.org/mediawiki/2015/4/4e/NUDT_CHINAmodelPNG6.png" style="width: 400px; height:auto"></td>
 +
</tr>
 +
<tr><td><p style = "font-size: 12px;">Figure4. The resultant quantity with two enzymes on one scaffold.</p></td></tr>
 +
</Table>
 +
</center>
 +
<p>With the distance between different enzymes sites on one scaffold enlarging, the the effect of the scaffold decreasing.</p>
 +
<p><B style = "color: #d82545">Overall Analysis: </B></p>
 +
<p>It has same probability between scaffold and none-scaffold design. when the substrate collision with the first enzyme. So, the substrates are consumed in nearly same speed.</p>
 +
<p>While because the scaffolds aggregate the enzymes, when the intermediate products try to collide with the second enzyme, it tends to consume less time between collision with enzyme. So, the scaffold can improve the multi-enzyme reaction efficiency.</p>
 +
<p>However, when the distance between enzyme sites to a extent, the scaffold can aggregate enzymes enough tight, the advantage of scaffold will disappear.</p>
 +
<p></p>
 +
<script type="text/javascript">
 +
$(document).ready(function(){
 +
$("#pos6").click(function(){
 +
$("#slide6").slideToggle(300);
 +
});
 +
});
 +
</script>
 +
</div>
 +
<!--Conclusion-->
 +
<h2 id = "pos7">VII.Conclusion<B style = "color: #d82545">(CLICK)</B></h2>
 +
<div class = "BLANK_Container" id = "slide3">
 +
<p>Based on our simulation, we came to the conclusion that:</p>
 +
<tr>
 +
<td><p style = 'padding: 0px 90px'>1. The TALE-based scaffold system can improve the multi-enzyme reaction efficiency.</p></td>
 +
</tr>
 +
<tr>
 +
<td><p style = 'padding: 0px 90px'>2. With the multi-enzyme reaction series increasing, the effect of the scaffold is brought out.</p></td>
 +
</tr>
 +
<tr>
 +
<td><p style = 'padding: 0px 90px'>3. With the distance between different enzymes sites on one scaffold enlarging, the the effect of the scaffold decreasing. (We did not consider the steric hindrance during modeling, thus this conclusion is not consistent with wet lab.)</p></td>
 +
</tr>
 +
<p></p>
 +
<script type="text/javascript">
 +
$(document).ready(function(){
 +
$("#pos7").click(function(){
 +
$("#slide7").slideToggle(300);
 +
});
 +
});
 +
</script>
 +
</div>
 +
<!--Further Study-->
 +
<h2 id = "pos8">VIII.Further Study<B style = "color: #d82545">(CLICK)</B></h2>
 +
<div class = "BLANK_Container" id = "slide8">
 +
<p>In the future, we will go along the road and improve this simple model.</p>
 +
<tr>
 +
<td><p style = 'padding: 0px 90px'>1. Optimizing the simulation algorithm and using more precise parameters.</p></td>
 +
</tr>
 +
<tr>
 +
<td><p style = 'padding: 0px 90px'>2. Building 3-dimension model.</p></td>
 +
</tr>
 +
<tr>
 +
<td><p style = 'padding: 0px 90px'>Considering non-contact intermolecular force into model (molecular field), which could simulate the steric hindrance.</p></td>
 +
</tr>
 +
<p></p>
 +
 
 +
<script type="text/javascript">
 +
$(document).ready(function(){
 +
$("#pos8").click(function(){
 +
$("#slide8").slideToggle(300);
 +
});
 +
});
 +
</script>
 +
</div>
 +
 
 +
 
 +
</div>
 +
 
 +
<!--Navigation-->
 +
<div id = "navigation">
 +
<img src="https://static.igem.org/mediawiki/2015/5/58/TEAM_NUDT_CHINA_iGEM.png"/>
 +
<li><a href="#myMainContainer" class = "t"><span>TOP/TIP</span></a></li>
 +
<li><a href="#pos1"><span>Abstract</span></a></li>
 +
<li><a href="#pos2"><span>Introduction</span></a></li>
 +
<li><a href="#pos3"><span>Simplifying</span></a></li>
 +
<li><a href="#pos31" class = 'b'><span>Object</span></a></li>
 +
<li><a href="#pos32" class = 'b'><span>Geometry</span></a></li>
 +
<li><a href="#pos33" class = 'b'><span>Motion</span></a></li>
 +
<li><a href="#pos34" class = 'b'><span>Interaction</span></a></li>
 +
<li><a href="#pos4"><span>Simu Environment</span></a></li>
 +
<li><a href="#pos5"><span>Parameters Setting</span></a></li>
 +
<li><a href="#pos6"><span>Result &amp; Analysis</span></a></li>
 +
<li><a href="#pos7"><span>Conclusion</span></a></li>
 +
<li><a href="#pos8"><span>Further Study</span></a></li>
 +
<img src="https://static.igem.org/mediawiki/2015/9/93/Team_NUDT_CHINA_Navigate.png"/>
 +
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<p>Copyright © 2015 NUDT_CHINA | Powered by Nianhao Xie</p>
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Revision as of 21:03, 18 September 2015

MODELING

TIPS1: The left MENU :) links to other NUDT_CHINA website.

TIPS2: The right NAVIGATE :) posites on content in this page. (Valid when UNFOLDED)

TIPS3: Click SUBTITLE to FOLD/UNFOLD related content.

I.Abstract(CLICK)

This model tries to prove theoretically the TALE-based scaffold system can improve the multi-enzyme reaction efficiency. (You can go PROJECT page to see more.) The core idea is to calculate reaction rate parameters using time driven stochastic simulation method, and compare these parameters of the TALE-based scaffold system and the none-scaffold system. Furthermore, the effect of the multi-enzyme sites on scaffold is studied.

II.Introduction(CLICK)

The models to study reaction efficiency are based on reaction molecular dynamics. The basic point of reaction molecular dynamics is that REACTION EQUALS COLLISION. Michaelis-Menten equation is universally applied to build reaction molecular dynamics models. However, although the Michaelis-Menten equation is derived from the collision behavior characteristics, it presumes that the reactant is UNIFORMLY dispersed in the reaction space and the COLLISION EQUALS CONCENTRATION. Therefore, the Michaelis-Menten equation is improper to simulate the scaffold “aggregation” effect where the reactant is UNEVEN.

Stochastic simulation can directly calculate the behavior of every reactant molecule, which can simulate scaffold “aggregation” effect. The idea of stochastic simulation is to transform a difficult question to a sampling question. In other words, in this article, the stochastic simulation method is applied to calculate and assess scaffold system and none-scaffold system parameters in the form of probability distributions.

Figure 1. The compare between two methodologies.

The stochastic simulation starts from COLLISION while the Michaelis-Menten equation basic on the CONCENTRATION. The transform from COLLISION to CONCENTRATION requires uniform condition.

III.Molecular Behavior & Simplifying Assumptions(CLICK)

We simulated multi-enzyme reaction in E.coli. Considering our limited time, equipment and abilities, we adopted the simplifying assumptions below.

Object

The involved objects are E.coli, reactants, scaffold and enzymes (on or off scaffolds). And the enzyme sites are fixed on scaffolds.

Geometry

The simulation is on two dimension. Thus, E.coli, reactants and enzymes are treated as circle, and the scaffolds are treated as lines.

(a) E.coli

(b) Simplified E.coli with scaffold

(c) Simplified E.coli without scaffold

Figure 2. The simplification of E.coli

Motion

The simulation is time driven. Enzymes and scaffolds are fixed in E.coli. The motion of substrates and intermediate products is the composition of the cyclosis and random thermal motion. We neglected the cyclosis here.

The random thermal motion makes them go forward to an uncertain direction. The motion direction and speed in a time step can decide the random thermal motion, where the direction and speed are uniformly distributed. We abandoned the more accurate Maxwell molecular velocity to improve the calculation speed by voiding probability integral of Maxwell distribution.

Interaction

All object are restricted to move within on E.coli. We neglect the non-contact intermolecular force. The substrates and intermediate products can overlap the enzyme and scaffold spot which can simulate the combination during reaction process.

The demo of the reactant motion and interaction (First 30 time units in 3000 time units)

Every collision (overlap) between reactant and enzyme is effective as long as the they match. And every reaction can be finished instantaneously as long as the collision happened.

The smaller blue dots are substrates and the larger blue and red dots are different enzyme. The different enzymes of (b) are linked by scaffold and the scaffold are independently dispersed while those in (c) are independently dispersed.

IV.Simulation Environment/Platform(CLICK)

MATLAB & MacBook Pro 2.8 GHz Intel Core i7

V.Parameters Setting(CLICK)

The simulation aims at comparing the scaffold and none-scaffold effect and studying the sites position (on scaffold) effect. The parameters setting below balanced the simulation similarity degree and calculation ability of our equipment. So the reactants, enzyme quantities cell diameter are smaller than the E.coli. But the density of reactants, enzyme is relatively near to the real condition.

Simulation Time Step 1
Simulation Total Time 2000
Reactant speed lower limit (times to reactant diameter) 0.3
Reactant speed upper limit (times to reactant diameter) 2
Scaffold Quantity 4
Initial Reactant Quantity 150
Reactant Diameter 3
Cell Diameter 200

Table.1 The Constant Parameters Setting

Enzyme Type Enzymes Distance Enzymes Diameter
Group 1 2 8 [6,8]
Group 2 2 16 [6,8]
Group 3 2 18 [6,8]
Group 4 3 [12,12] [6,8,10]

Table.2 The Variable Parameters Setting

Graphic Note

VI.Result & Analysis(CLICK)

The multi-enzyme reaction series is:

Note1: Return to V.Parameter Setting to see detailed parameter of the group below.

Note2: All movies are the first 30 time units in 3000 time units.

Group 1

Analysis: Although the substrates are consumed in similar speed. With scaffold the, the intermediate products are transformed to resultant faster than that without scaffold. Thus, the scaffold design improves the reaction efficiency.

Group 2

Analysis: The distance between enzyme sites is larger than group1. But, similarly, the substrates are consumed in nearly same speed. With scaffold the, the intermediate products are transformed to resultant faster than that without scaffold. Thus, the scaffold design improves the reaction efficiency.

Group 3

Analysis: The distance between enzyme sites is enlarged on. Differently, the scaffold design and none-scaffold design have similar reaction efficiency.

Group 4

Analysis: The multi-enzyme reaction series increases than that above. The substrates are also consumed in nearly same speed. But the effect of the scaffold is more obvious than that above.

Group 1/2/3

Figure4. The resultant quantity with two enzymes on one scaffold.

With the distance between different enzymes sites on one scaffold enlarging, the the effect of the scaffold decreasing.

Overall Analysis:

It has same probability between scaffold and none-scaffold design. when the substrate collision with the first enzyme. So, the substrates are consumed in nearly same speed.

While because the scaffolds aggregate the enzymes, when the intermediate products try to collide with the second enzyme, it tends to consume less time between collision with enzyme. So, the scaffold can improve the multi-enzyme reaction efficiency.

However, when the distance between enzyme sites to a extent, the scaffold can aggregate enzymes enough tight, the advantage of scaffold will disappear.

VII.Conclusion(CLICK)

Based on our simulation, we came to the conclusion that:

1. The TALE-based scaffold system can improve the multi-enzyme reaction efficiency.

2. With the multi-enzyme reaction series increasing, the effect of the scaffold is brought out.

3. With the distance between different enzymes sites on one scaffold enlarging, the the effect of the scaffold decreasing. (We did not consider the steric hindrance during modeling, thus this conclusion is not consistent with wet lab.)

VIII.Further Study(CLICK)

In the future, we will go along the road and improve this simple model.

1. Optimizing the simulation algorithm and using more precise parameters.

2. Building 3-dimension model.

Considering non-contact intermolecular force into model (molecular field), which could simulate the steric hindrance.