A Model for Simulating Hypothetical Protein Crystallization Behaviors

This paper describes the development of an approximate physical model that can be used for generating diierent types of protein crystallization behaviors or responses in varying physico-chemical environments. The modeling process involves three stages, two of which have been completed. The model developed in Stage I was over-simpliied and was aimed at providing the right computational avor of the process of vapor diiusion that is a generally used technique for macromolecular crystallization. After this model was thoroughly tested, we enhanced the simple model to include a more elaborate nucleation theory, that still is an approximation of the actual physical chemistry involved. This stage II model was evaluated and found to have face validity in that it is possible to simulate diierent types of protein response behaviors-for example , proteins that crystallize easily under a broad range of conditions, proteins that crystallize under a narrow range of conditions, and proteins that take a very long time to nucleate and grow. It took approximately two years to complete stages I and II. Stage III would be much more elaborate and would involve the justiication of all the equations in the model rigorously from a physical chemistry point of view. This could take a fair amount of time, as actual experimentation will need to be performed.