Exploring the natural conformational changes of the C-terminal domain of calmodulin.

Several experimental results suggest that the Ca2+-loaded C-terminal domain of calmodulin (or some of its mutants) exhibits conformational changes triggered solely by thermal fluctuations. The time scales involved are in the 10(-6)-10(-3) s range. Here we develop a theoretical method to explore this type of motions based on a modified version of molecular dynamics algorithm where the secondary structure motifs are held fixed. In this version, increasing the temperature enhances the sampling of conformations with locally fixed secondary structures. From the temperature dependence of the transition rate between various conformational states, we obtain characteristic times that are consistent with those observed experimentally.