Theory 02/Protein conformational ensembles/Cryo-electron microscopy
Ensembles Are Wider Than Structures
A protein's functional range of motion is set by the ratio of thermal energy to the stiffness of its slowest mode, so two proteins with identical ground-state structures can have very different accessible ensembles.
01Mechanism
The slowest collective mode dominates the amplitude; stiffness in that mode determines how far the protein wanders at physiological temperature.
02Prediction
Ensemble width should track soft-mode stiffness.
03Refutation
Identical class distributions for proteins of different softness would remove the link.
04What makes it checkable
Cryo-EM now resolves multiple conformational classes within one sample, and the width of the distribution can be measured rather than inferred. A protein with a soft slow mode will show more classes at the same resolution.
05Why it was not testable before
Crystallography gave one structure per protein; the ensemble was a theoretical convenience until cryo-EM could image it.