Computational Strategies
Computational analyses of intracellular signaling 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 simulator capable of incorporating diffusion and chemical reactions in inhomogeneous media.