  Rigid-body motions of protein secondary structure are often implicated in
mecha-nisms of protein function. In GPCRs, evidence suggests that intracellular
loop 2 (IL2) contains a segment characterized as a helix when the activated
receptor trig-gers downstream signaling. However, neither experimental nor
computational methods are readily available to assess quantitatively the degree
of collective mo-tions in such secondary structure motifs of proteins. Here we
describe a new el-ement of our N-body Information Theory (NbIT) framework to
address this problem. To this end we introduce total intercorrelation, a
measure in infor-mation theory that can be used to describe n-body correlated
dynamics between multivariate distributions, such as 3-dimensional atomic
fluctuations in simula-tions of proteins. We also define two additional
measures, the rigid-body fraction and correlation order, which can be
determined from the decomposition of the configurational entropy. Using these
measures, we analyze the dynamics of IL2 in microsecond Molecular Dynamics
simulations of the 5-HT2A receptor to demonstrate the powerful features of the
new analysis techniques in studying the collective motion dynamics of secondary
structure motifs. The analysis reveals an intriguing difference in the extent
of correlated motions in the helical segment of IL2 in the presence and absence
of bound 5-HT, the endogenous agonist that ac-tivates the receptor and triggers
downstream signaling, suggesting that IL2 rigid-body motions can display
distinct behaviors that may discriminate functional mechanism of GPCRs.
