Computational analyses of intracellular signalling provide an overlying framework in which the previous three lines of experimental investigation are consolidated.

We are developing a detailed quantitative model of the postsynaptic signaling system that encompasses:

1.   biophysical measurements of the binding constants between proteins,

2.   diffusion and translocation of proteins, and

3.   intracellular geometric constraints,

all confined in the boundary established by the postsynaptic spine.

A tenet of our computational efforts is that intracellular signaling cannot be accurately represented with ordinary differential equation approaches. The laws of mass action cannot accurately represent the behavior of a small number of reactants in a compartment like the postsynaptic spine. Additionally, the intracellular space is neither homogenous nor well mixed. Accurately capturing these features requires novel computational strategies.

A present focus is the construction and validation of a general purpose Monte Carlo simulator capable of incorporating diffusion and chemical reactions in inhomogeneous media.

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