Observation time scale, free-energy landscapes, and molecular symmetry

Significance This work explains how the experimental time scale determines our perception of the free-energy landscape for a molecular system. Greater temporal resolution naturally resolves more free-energy minima, although this structure may be averaged out over longer time scales. Hence shorter observation times may resolve more states, but result in broken ergodicity. A consistent treatment of the thermodynamics that corresponds with a given experiment must therefore account for the feasibility of different rearrangement mechanisms on the relevant observation time scale. Hence we establish a connection between the concepts of molecular symmetry, ergodicity, and local equilibrium.