The theory of frame ordering: observing motions in calmodulin complexes

Abstract

Large scale functional motions of molecules are studied experimentally using numerousmolecular and biophysics techniques, the data from which are subsequently interpretedusing diverse models of Brownian molecular dynamics. To unify all rotational physics tech-niques and motional models, the frame order tensor–a universal statistical mechanics theorybased on the rotational ordering of rigid body frames–is herein formulated. The frame order-ing is the fundamental physics that governs how motions modulate rotational molecular phys-ics and it defines the properties and maximum information content encoded in the observablephysics. Using the tensor to link residual dipolar couplings and pseudo-contact shifts, two dis-tinct information-rich and atomic-level biophysical measurements from the field of nuclearmagnetic resonance spectroscopy, to a number of basic mechanical joint models, a highlydynamic state of calmodulin (CaM) bound to a target peptide in a tightly closed conformationwas observed. Intra- and inter-domain motions reveal the CaM complex to be entropicallyprimed for peptide release.