  The key to understanding a protein's function often lies in its
conformational dynamics. We develop a coarse-grained variational model to
investigate the interplay between structural transitions, conformational
flexibility and function of N-terminal calmodulin (nCaM) domain. In this model,
two energy basins corresponding to the ``closed'' apo conformation and ``open''
holo conformation of nCaM domain are connected by a uniform interpolation
parameter. The resulting detailed transition route from our model is largely
consistent with the recently proposed EF$\beta$-scaffold mechanism in EF-hand
family proteins. We find that the N-terminal part in calcium binding loops I
and II shows higher flexibility than the C-terminal part which form this
EF$\beta$-scaffold structure. The structural transition of binding loops I and
II are compared in detail. Our model predicts that binding loop II, with higher
flexibility and early structural change than binding loop I, dominates the
conformational transition in nCaM domain.
