Biomod/2012/TeamSendai/Simulation

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<div id="Container">
<div id="Container">
      
      
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<h1>Project</h1>
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<!-- Menu -->
 +
<ul id="menu">
 +
<li><a href="http://openwetware.org/wiki/Biomod/2012/Tohoku/Team_Sendai ">Top</a></li>
 +
<li><a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Idea ">Project</a></li>
 +
<li><a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Simulation">Simulation</a>
 +
</li>
 +
<li><a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Design">Design</a>
 +
</li>
 +
<li>
 +
<a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Experiment ">Experiment</a>
 +
<ul>
 +
<li><a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Method">Method</a>
 +
<ul>
 +
<li>
 +
<a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Result#Porter">Porter</a>
 +
<li>
 +
<a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Result#Cylinder">Cylinder</a> </li>
 +
<li> <a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Result# Vesicle">Vesicle</a>
 +
</li>
 +
</ul>
 +
</li>
 +
<li>
 +
<a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Result">Result</a>
 +
<ul>
 +
<li>
 +
<a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Result#Porter">Porter</a>
 +
<li>
 +
<a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Result#Cylinder">Cylinder</a> </li>
 +
<li> <a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Result# Vesicle">Vesicle</a>
 +
</li>
 +
</ul>
 +
</li>
 +
</ul>
 +
</li>
 +
<li>
 +
<a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Achievement">Achievement</a>
 +
</li>
 +
<li>
 +
<a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Diary">Diary</a>
 +
</li>
 +
<li>
 +
<a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/Team ">Team</a>
 +
</li>
 +
<li>
 +
<a href=" http://openwetware.org/wiki/Biomod/2012/TeamSendai/FAQ">FAQ</a>
 +
</li>
 +
</ul>
 +
 
 +
<!--目次 -->
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<div id="mokuji">
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<h2>Contents</h2>
 +
<ol>
 +
<li><a href="#Numerical Calculation for Electric Potential">Electric Potential Numerical Calculation</a></li>
 +
<ol>
 +
<li><a href="#Model">Model</a></li>
 +
<li><a href="#">Results</a></li>
 +
</ol>
 +
 
 +
<li><a href="#MD Simulation">MD Simulation</a></li>
 +
<ol>
 +
<li><a href="#DNA Model">DNA Model</a></li>
 +
<ol>
 +
<li><a href="#Results">Results</a></li>
 +
</ol>
 +
 
 +
<li><a href="#Comparison of capture ability">Comparison of capture ability</a></li>
 +
<ol>
 +
<li><a href="#Results">Results</a></li>
 +
</ol>
 +
<li><a href="#Reference">Reference</a></li>
 +
</ol>
 +
 
 +
</ol>
 +
</div>
 +
 
<p>
<p>
-
Our project is to create a new designable channel with a high selectivity and activity. We named the channel; Cell Gate. (Cell Gateが出てくるのが唐突だと思う) We make the Cell Gate of DNA.
+
<br><br>
-
</p>
+
-
<h1>Why do we use DNA?</h1>
+
 
 +
 
 +
</p>
 +
<a name="Numerical Calculation"></a><h2>Numerical Calculation</h2>
<p>
<p>
-
・自然界にあるチャネルは(タンパク質でできていて?)人間の手で作り変えたりして自在に扱うということは難しい。だから、デザインが可能でsiRNAなどの生体分子と相互作用を持つDNAを使って、チャネルを作ることができれば、チャネル設計(?)の幅が広がるというようなことをまとめていただけると…。(タンパク質とDNAの対比表とか対比図があるとわかりやすい)
+
 
 +
A phosphodiester bond make up the backbone of each helical strand of DNA. <br>
 +
The phosphate groups in the phosphodiester bond are negatively-charged.<br>
 +
Because gate is produced by DNA, we can not ignore the influence of the Coulomb force.<br>
 +
So we calculate the electric potential near the gate.
 +
 
</p>
</p>
-
<h1>How do we penetrate the Gate to membrane?</h1>
+
<a name="Model"></a><h2>Model</h2>
-
<img src=" http://openwetware.org/images/e/e6/Format_gate_no_tukikata_project.jpg " alt="coreste&tutu " align="left" width="450px" height="290px" >
+
<p>
<p>
-
Lipidと親和性のあるコレステロールを使えばいいということを面白おかしく論理的に説明.
+
<br>
-
どのように貫通するかなど。</br>
+
Sets the coordinates as follows.<br>
-
(画像はプレゼン用のを拝借したので修正必要。特にHexagonalとかsmall tube とか。絵自体もまだまだ分かりやすくできそうな気が。数式みたいな絵じゃなく、もっと動きのあるものに(アニメーションにしろというわけではない))
+
 
-
<br clear="left">
+
<img src="http://openwetware.org/images/9/90/Cy.png" width="350px" height="300px">
 +
<img src="http://openwetware.org/images/6/66/Lin.jpg" width="420px" height="300px"><br>
 +
<br><br><br>
 +
 
 +
Point-charge model is used.<br>
 +
Assumesd the phosphate groups negative charge,and<br>
 +
negative charge circles the axis of the double helix once every 10.4 base pairs like DNA.<br>
 +
 
 +
And we use follow fomula to calculate electric potential.<br><br>
 +
Debye–Hückel equation<br>
 +
<img src="http://openwetware.org/images/e/ec/Potential_fomula.png" width="300px" height="90px"><br>
 +
<br>
 +
Debye length<br>
 +
<img src="http://openwetware.org/images/f/f9/Debyelen.png" width="400px" height="250px"><br><br>
 +
 
 +
 
 +
 
 +
 
 +
Add all potential by negative charge DNA which compose gate have.<br>
 +
(used C language to output the numbers)<br><br>
 +
<img src="http://openwetware.org/images/4/45/Helix.gif" width="500px" height="290px"><br>
 +
 
 +
 
 +
 
 +
Condition<br>
 +
Temperature 298[K]<br>
 +
Na+ 50mM<br>
 +
 
 +
<img src="http://openwetware.org/images/f/fc/Add2.png" width="500px" height="180px"><br>
 +
 
 +
 
 +
 
</p>
</p>
-
<h1>穴開けただけでチャネル(細胞膜間輸送?)って呼べるの?</h1>
+
<a name="Results"></a><h2>Results</h2>
<p>
<p>
-
クーロン力があるから物質だだ漏れにはならない。Gateの内部にDNAの一本鎖並べて、DNAの特異性を利用することで、狙いの分子だけを、一本鎖DNAとの結合エネルギーポテンシャルの坂道に乗せることができる。その一本鎖DNAの列をPoaterと呼ぶことにする。PorterがCellGateのエンジン。みたいなことをうまくまとめる。ここでPorterの説明を終えるつもりで。画像に関してはとりあえず津沢のポテンシャルエネルギーのグラフは必須。
+
<br>
 +
Electric potential changing z-axis at x-axis and y-axis is 0.<br>
 +
 
 +
<img src="http://openwetware.org/images/0/09/1014x0y0potential.png" width="620px" height="450px"><br>
 +
the length of the gate is 88bp, 30nm.
 +
 
 +
Target base pair 25 を点電荷と仮定する
</p>
</p>
-
<h1>クーロン力があるならGateに近づけないんじゃない?</h1>
+
 
 +
<a name="MD Simulation"></a><h2>MD Simulation</h2>
<p>
<p>
-
Porterの一番目を伸ばせばいいみたいなことをキャッチ―な図とともに。筒井さんのシミュレーション映像を貼る。
+
We carried out molecular dynamics simulation to examine the the mechanism and
 +
the effectiveness of our structure “Cell Gate”.
 +
 
</p>
</p>
-
<h1>私たちが実験で目指したもの</h1>
+
<a name="DNA Model"></a><h2>DNA Model</h2>
-
<img src=" http://openwetware.org/images/c/c8/Format_cell_gate.jpg " alt="hybrid graph" align="left" width="465px" height="315px" >
+
<p>
<p>
-
ここで初めてMembrane登場? 細胞のモデルとして使っただけ?本物の細胞どうして使わなかったのかという疑問が生まれそう。何かいい理由はないものか。画像はプレゼン用のやつそのままなので改善の余地あり
+
For simplicity, course-grained DNA model is used in our simulation. <br>
 +
One DNA nucleotide is represented by one bead in the model and each bead can be<br>
 +
hybridized with complementary bead.<br>
 +
  <<モデル載せる>><br><br>
 +
The potential energy of the system includes 5 distinct contributions.<br>
 +
  <<ポテンシャル載せる>><br><br><br>
 +
The first three terms are intramolecular interactions , bonds , bond angles, and<br>
 +
dihedral angles. In order to express “tether like structure”, only bond interactions<br>
 +
are active in our DNA model.<br>
 +
And the latter two are non-bonded interactions. Coulomb interactions are taken into<br>
 +
account using the Debye-Huckel approximation which enables to internalize<br>
 +
counterions contribution.<br>
 +
Constants of these potentials are achieved from references.<br>
 +
The force on bead i is given by a Langevin equation<br><br><br>
 +
 
 +
Langevin equation<br><br>
 +
 +
<img src="http://openwetware.org/images/1/11/Langevin.png" width="220px" height="80px"><br><br>
 +
<img src="http://openwetware.org/images/2/23/F%3D.png" width="150px" height="80px"><br>
 +
 
 +
The first term donates a conservative force derived from the potential U and the<br>
 +
second is a viscosity dependent friction.<br>
 +
The third term is a white Gaussian noise and effects of solvent molecules are<br>
 +
internalized in this term.<br>
 +
Langevin equation is integrated using a Velocity-Verlet method.<br><br><br>
 +
Toehold displacement of dsDNA<br>
 +
In order to test predictive capability of the model, here we carried out a simulation<br>
 +
of Toehold displacement between two strands.<br>
 +
Length of strands and simulation situation was as follows.<br><br>
 +
Target strand/Toehold A/Toehold B : 25nt / 9nt (+10nt spacer) / 13nt (+10nt
 +
spacer)<br>
 +
Temperature : 300K<br>
 +
Time-step size / simulation length : 0.01ps / 100ns<br>
 +
Ion concentration : 50mM Na+<br><br>
 +
results<br>
 +
<<後ほど>>
 +
 
</p>
</p>
-
<br clear="left">
+
<a name="Comparison of capture ability"></a><h2>Comparison of capture ability</h2>
 +
<p>
 +
One of constructional features of our structure ”Cell-Gate” is the use of new strand
 +
displacement method.<br>
 +
By comparing our selector strand and a toehold strand, the most popular method for<br>
 +
strand displacement, we show the effectiveness our structure in terms of capture
 +
ability.<br><br><br>
 +
Model and Method<br>
 +
According to the design of experiment section, we designed models as below of the<br>
 +
selector strand and the toehold strand.<br>
 +
<<モデル載せる>><br><br><br>
 +
Hex-cylinder is represented as the assembly of electrically-charged mass points<br>
 +
fixed on the field.<br>
 +
<<モデル載せる>><br><br><br>
 +
Simulation was carried out at the following condition.<br>
 +
Temperature : 300K<br>
 +
Ion concentration : Na+ 50mM<br>
 +
Box size : 20nm×20nm×20nm (periodic boundary condition)<br>
 +
Time-step size / simulation length : 0.01ps / 10ns<br>
 +
Results<br>
 +
<<後ほど>><br>
 +
 
</p>
</p>
-
<h1>Application in future</h1>
+
<a name="Reference"></a><h2>Reference</h2>
<p>
<p>
-
あんなことやこんなことに使えるというのを図入りで。
+
1. Thomas A. Knotts et al. A coarse grain model of DNA , J.Chem.Phys
 +
126,084901(2007)<br>
 +
2. Carsten Svaneborg et al. DNA Self-Assembly and Computation Studied with a
 +
Coarse-Grained Dynamic Bonded Model, DNA 18,LNCS 7433, pp.123-134,
 +
2012<br>
 +
3. Xhuysn Guo & D.Thirumalai, Kinetics of Protein Folding: Nucleation
 +
Mechanism, Time Scales, and Pathways, Biopolymars, Vol.36, 83-102 (1995)<br>
 +
4. GROMACS manual ()<br>
 +
5. Cafemol manual ( http://www.cafemol.org/ )<br>
 +
 
</p>
</p>
 +
</div>
</div>
</body>
</body>
</html>
</html>

Revision as of 11:22, 24 October 2012

Team Sendai Top



Numerical Calculation

A phosphodiester bond make up the backbone of each helical strand of DNA.
The phosphate groups in the phosphodiester bond are negatively-charged.
Because gate is produced by DNA, we can not ignore the influence of the Coulomb force.
So we calculate the electric potential near the gate.

Model


Sets the coordinates as follows.




Point-charge model is used.
Assumesd the phosphate groups negative charge,and
negative charge circles the axis of the double helix once every 10.4 base pairs like DNA.
And we use follow fomula to calculate electric potential.

Debye–Hückel equation


Debye length


Add all potential by negative charge DNA which compose gate have.
(used C language to output the numbers)


Condition
Temperature 298[K]
Na+ 50mM

Results


Electric potential changing z-axis at x-axis and y-axis is 0.

the length of the gate is 88bp, 30nm. Target base pair 25 を点電荷と仮定する

MD Simulation

We carried out molecular dynamics simulation to examine the the mechanism and the effectiveness of our structure “Cell Gate”.

DNA Model

For simplicity, course-grained DNA model is used in our simulation.
One DNA nucleotide is represented by one bead in the model and each bead can be
hybridized with complementary bead.
  <<モデル載せる>>

The potential energy of the system includes 5 distinct contributions.
  <<ポテンシャル載せる>>


The first three terms are intramolecular interactions , bonds , bond angles, and
dihedral angles. In order to express “tether like structure”, only bond interactions
are active in our DNA model.
And the latter two are non-bonded interactions. Coulomb interactions are taken into
account using the Debye-Huckel approximation which enables to internalize
counterions contribution.
Constants of these potentials are achieved from references.
The force on bead i is given by a Langevin equation


Langevin equation




The first term donates a conservative force derived from the potential U and the
second is a viscosity dependent friction.
The third term is a white Gaussian noise and effects of solvent molecules are
internalized in this term.
Langevin equation is integrated using a Velocity-Verlet method.


Toehold displacement of dsDNA
In order to test predictive capability of the model, here we carried out a simulation
of Toehold displacement between two strands.
Length of strands and simulation situation was as follows.

Target strand/Toehold A/Toehold B : 25nt / 9nt (+10nt spacer) / 13nt (+10nt spacer)
Temperature : 300K
Time-step size / simulation length : 0.01ps / 100ns
Ion concentration : 50mM Na+

results
<<後ほど>>

Comparison of capture ability

One of constructional features of our structure ”Cell-Gate” is the use of new strand displacement method.
By comparing our selector strand and a toehold strand, the most popular method for
strand displacement, we show the effectiveness our structure in terms of capture ability.


Model and Method
According to the design of experiment section, we designed models as below of the
selector strand and the toehold strand.
<<モデル載せる>>


Hex-cylinder is represented as the assembly of electrically-charged mass points
fixed on the field.
<<モデル載せる>>


Simulation was carried out at the following condition.
Temperature : 300K
Ion concentration : Na+ 50mM
Box size : 20nm×20nm×20nm (periodic boundary condition)
Time-step size / simulation length : 0.01ps / 10ns
Results
<<後ほど>>

Reference

1. Thomas A. Knotts et al. A coarse grain model of DNA , J.Chem.Phys 126,084901(2007)
2. Carsten Svaneborg et al. DNA Self-Assembly and Computation Studied with a Coarse-Grained Dynamic Bonded Model, DNA 18,LNCS 7433, pp.123-134, 2012
3. Xhuysn Guo & D.Thirumalai, Kinetics of Protein Folding: Nucleation Mechanism, Time Scales, and Pathways, Biopolymars, Vol.36, 83-102 (1995)
4. GROMACS manual ()
5. Cafemol manual ( http://www.cafemol.org/ )

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