  We introduce an approach for performing "very long" computer simulations of
the dynamics of simplified, folded proteins. Using an alpha-carbon protein
model and a fine grid to mimic continuum computations at increased speed, we
perform unbiased simulations which exhibit many large-scale conformational
transitions at low cost. In the case of the 72-residue N-terminal domain of
calmodulin, the approach yields structural transitions between the calcium-free
and calcium-bound structures at a rate of roughly one per day on a single Intel
processor. Stable intermediates can be clearly characterized. The model employs
Go-like interactions to stabilize two (or more) experimentally-determined
structures. The approach is trivially parallelizable and readily generalizes to
more complex potentials at minimal cost.
