# Biomod/2012/TeamSendai/Simulation

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Numerical Calculation

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Aim of Simulation

- 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 made of DNA, we can not ignore the influence of the Coulomb force. So we calculate the electric potential inside and outside the GATE. + The phosphate groups in the backbone of DNA are negatively-charged. Because GATE is made of DNA, we can not ignore the influence of the Coulomb force. So we calculate the electric potential inside and outside the GATE. -

Model

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Model of DNA

- The coodinates are set as follows: + [[Image: Cy.png |200px]] [[Image: Cy.png |200px]] [[Image: Lin.jpg |200px]] [[Image: Lin.jpg |200px]] Line 14: Line 13: [[Image: Helix.gif |left|500px|thumb| Condition: Temperature 298[K], Na+ 50mM]] [[Image: Helix.gif |left|500px|thumb| Condition: Temperature 298[K], Na+ 50mM]] {{-}} {{-}} - A point-charge model is used. We assume the phosphate groups have negative charge,and negative charge circles the axis of the double helix once every 10.4 base pairs. we use following fomulas to calculate electric potential. + A point-charge model is applied to DNA model. We assume the phosphate groups have negative charge,and negative charge circles the axis of the double helix once every 10.4 base pairs. we use following fomulas to calculate electric potential. Debye–Hückel equation: Debye–Hückel equation: Line 25: Line 24: {{-}} {{-}} - Summing up all the Electric Potential for every DNA phosphate presented on the DNA origami GATE. (used C language to output the numbers)

Results

Results

+ Summing up all the Electric Potential for every DNA phosphate presented on the DNA origami GATE. (used C language to output the numbers) + Electric potential at the z-axis(x=0, y=0). Electric potential at the z-axis(x=0, y=0). [[Image: 1014x0y0potential.png |right|300px]] [[Image: 1014x0y0potential.png |right|300px]]

Team Sendai Top

# Aim of Simulation

The phosphate groups in the backbone of DNA are negatively-charged. Because GATE is made of DNA, we can not ignore the influence of the Coulomb force. So we calculate the electric potential inside and outside the GATE.

## Model of DNA

Condition: Temperature 298[K], Na+ 50mM

A point-charge model is applied to DNA model. We assume the phosphate groups have negative charge,and negative charge circles the axis of the double helix once every 10.4 base pairs. we use following fomulas to calculate electric potential.

Debye–Hückel equation:

Debye length

## Results

Summing up all the Electric Potential for every DNA phosphate presented on the DNA origami GATE. (used C language to output the numbers)

Electric potential at the z-axis(x=0, y=0).

the length of the gate is 88bp, 30nm. Target base pair 25 を点電荷と仮定する もっときれいなグラフに出力できないか

# MD Simulation

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

## DNA Model

For simplicity, a 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 a complementary bead.

The potential energy of the system includes 5 distinct contributions.

The first three terms are intramolecular interactions, bonds, bond angles, and dihedral angles. In order to express the “tether like structure”, only bond interactions are considered in our DNA model.

And the latter two terms are non-bonded interactions. Coulomb interactions are taken into account using the Debye-Huckel approximation which enables to internalize counterions contribution.

Parameters of these potentials were fit to the reference literature ; Thomas A. Knotts et al. A coarse grain model of DNA .

The force on bead i is given by a Langevin equation

The first term donates a conservative force derived from the potential Vtot and the second is a viscosity dependent friction.

The third term is a white Gaussian noise and effects of collision with solvent molecules which causes brownian motion are internalized in this term.

Langevin equation is integrated using a Velocity-Verlet method.

## Toehold displacement of dsDNA

In order to test the model, here we carried out a simulation of Toehold displacement between two strands.

Length of strands and simulation condition were as follows:

Target strand / Toehold A / Toehold B : 16nt / 9nt / 13nt
Temperature : 300K
Time-step / simulation length : 0.01ps / 100ns
Ion concentration : 50mM Na+

### Results

 Movie1 : MD simulation of toehold strand displacement

Movie 1 shows the trajectory of each strand from the simulation. The target strand moves from Toehold A strand to Toehold B strand which are fixed on the field. This result agrees with the energy gradient.

## Comparison of capture ability

One of constructional features of our structure ”Cell-Gate” is the use of a novel strand displacement method.

By comparing our selector strand to toehold strand, the most popular method for strand displacement, we looked at the effectiveness of our structure in terms of it's strand capturing ability.

### Model and Method

According to the design of the experiment section, we modeled the selector strand and the toehold strand as shown below.

Hex-cylinder is represented as the assembly of fixed electrically-charged mass points.

Simulation was carried out at the following condition:

Temperature : 300K
Ion concentration : Na+ 50mM
Box size : 20nm×20nm×20nm (periodic boundary condition)
Time-step / simulation length : 0.01ps / 10ns

### Results and Conclusion

 Movie2 : MD simulation of porter strand Movie3 : MD simulation of toehold strand

Movie2 and 3 shows the result of each simulation, selector-target and toehold-target.

We note that this simulation was carried out under a periodic boundary condition, where the size of the simulation box is 20nm×20nm×20nm. Then, the distance between the target strand and the Hex-cylinder is maintained virtually constant.

One of the advantages of the selector strand is shrinking ability. The selector strand hybridizes to the target making a loop which makes it possible to extend the strand length without changing the final structure's length.

Results obtained from this simulation show that the selector strand can catch the target strand exists outside of the Hex-cylinder and hybridize completely while the toehold strand never hybridize to the target strand in simulation time.

We run 5 simulations for each capturing mechanism under the same conditions and results were almost the same as we first obtained.

By considering results of electrostatic potential calculation around the hex-cylinder and MD simulation, it is clear that the electrostatic field prevents the entrance of DNA strands into the Hex-cylinder and the selector strand helps it to get into the cylinder.

Therefore, we concluded that our novel selector strand provides a high capture ability to our system “Cell-Gate”.

## References

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 ( http://www.gromacs.org/ )

5. Cafemol manual ( http://www.cafemol.org/ )