3.8 Molecular Dynamics of Membrane Protein and Receptor Protein Binding

Collaborators : Christina Vasilakis (University of Illinois at Chicago), Edwin Westbrook (Argonne National Laboratory).

The cholera toxin is a mysterious and, until recently, elusive macromolecule which has infected and killed people for the past 150 years. Treatment of cholera would be aided by a thorough understanding of the mechanisms by which the toxin infects and quickly destroys a membrane. In order to begin to tackle this question, the structure of the bacterial protein must be solved [gibbsons]. Edwin Westbrook, our collaborator in this project, is one of the pioneers in solving the structure of the cholera toxin. His research results describe the cholera toxin structure and its dynamics. Still unsolved however is the problem of how the cholera toxin invades the external membrane of a healthy cell.

3.8.1 CAVE Visualization

This project uses the CAVE as a visualization tool to gain an understanding of the how the cholera toxin invades the cell's membrane. The application depicts a possible theory of how the cholera toxin transports an intact protein through a target cell's external membrane while intoxicating the cell. The cholera toxin is represented in terms of two basic structures: a red donut-shaped unit representing the receptor binding domain and a smaller yellow drop-shaped unit representing the active toxine enzyme. Figure 10 shows the cholera structure and the cell membrane. The colors are arbitrary and help the viewer distinguish between the two main components.

figure 10

The CAVE viewer witnesses the two stage process of the infection of a membrane. The first stage, the recognition process, occurs when the toxin approaches the target cell and finds a place where it can successfully attach itself, as can be seen in Figure 11. Once the molecule has ``docked'', it begins the second and lethal stage of infection by penetration. Once the yellow enzyme is inside the cell, a chain of events is fired, which will lead to dehydration and eventually death of the infected person.

figure 11

3.8.2 Discussion

This view of the transportation of the cholera toxin can be studied from a new and otherwise not so easily accessible point of view by virtue of the CAVE. The viewers can walk around the target area of the membrane and examine it. They can also experience the entire two stage process described above by walking around the target area, watching the binding domain approach the cell layer, and especially by peering through the hole through which the toxin penetrates and enters the cell membrane. The viewer can watch the entire process from either above or below the membrane, or even stand in the middle of it. The most common way viewers watched the simulation at the SIGGRAPH'92 conference was by alternating the views from above and below the membrane. They also reported that, in this way, they most strongly experienced the three dimensionality of the structures.

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