Unbiased simulation of structural transitions in calmodulin

Abstract

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.