Team:TU-Eindhoven/Model/2D Simulation

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Simulation in 2D

In the simulation three different constructs are present (Figure 1), which can move and rotate in accordance with a Monte Carlo algorithm. The first construct, the Scaffold Construct, consists of the parts of the Protein Scaffold were the inducer is already bound. The parts of the same construct can move separately, but with some restriction. The restrictions include the limitation of the distance between the parts and that the movement should be energetically possible. The other two parts (Center Point and Binding Partner) are connected and form the Binding Construct. There is a Center Point and at this Center Point, four Binding Partner parts can bind. The Binding Partners are also flexibly connected to the Center Point part, with the same restrictions as mentioned before.

Figure 1: Legend of the 2D simulation parts

In the legend you can see how the three different parts are visualized during the simulation. If a complex is formed, the Binding Partners should bind to the Protein Scaffold at the same orientation. An example of a complex can be seen in Figure 2.

Figure 2: Bond formation during the 2D simulation, when the Scaffold and Binding Partner have the right orientation to make contact

Before the simulation is executed, some parameters need to be defined.

Size of the simulation box

Number of steps in the simulation

Temperature

Valence

Of the Scaffold Construct

Of the Binding Construct

Length of the Linker (maximum distance between parts of the same construct)

Of the Scaffold Construct

Of the Binding Construct

Amount of Constructs

Of the Scaffold

Of the Binding Partner

Interactions between the parts

With the solvent

If the parts can form a complex

If scaffold and binding parts are next to each other and have the right orientation for complex formation, but are not at the correct position

If scaffold and binding parts are next to each other and do not have the right orientation for complex formation

After setting all these parameters, the simulation can be executed. The simulation is done with Matlab, for which we defined a script and several functions to make the code clear and efficient.

Watch the two movies below to see examples of a 2D simulation. The first movie is a simulation with a low concentrations of proteins and the second is a simulation with a larger simulation box, higher concentrations of the proteins and a longer simulation time.

As the simulation has only two dimensions, it is not accurate enough to simulate the constructs that we have designed. The scripts can be extended to a 3D simulation, but running a simulation like this would require a long computational time and much memory. Therefore, we choose to use another method (rule-based-modeling) for modeling the designed protein constructs.

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