2022 article

Non-ergodicity of a globular protein extending beyond its functional timescale

Li, J., Xie, J. F., Godec, A., Weninger, K. R., Liu, C., Smith, J. C., & Hong, L. (2022, August 4). CHEMICAL SCIENCE, Vol. 8.

By: J. Li *, J. Xie*, A. Godec *, K. Weninger n , C. Liu *, J. Smith *, L. Hong *

TL;DR: By performing single-molecule fluorescence resonance energy transfer experiments and molecular dynamics simulations of a multi-domain globular protein, cytoplasmic protein-tyrosine phosphatase (SHP2), it is demonstrated that the functional inter-domain motion is observationally non-ergodic over the time spans 10−12 to 10−7 s and 10−1 to 102 s. (via Semantic Scholar)
UN Sustainable Development Goals Color Wheel
UN Sustainable Development Goal Categories
7. Affordable and Clean Energy (OpenAlex)
Source: Web Of Science
Added: August 22, 2022

Internal motions of folded proteins have been assumed to be ergodic, i.e., that the dynamics of a single protein molecule averaged over a very long time resembles that of an ensemble. Here, by performing single-molecule fluorescence resonance energy transfer (smFRET) experiments and molecular dynamics (MD) simulations of a multi-domain globular protein, cytoplasmic protein-tyrosine phosphatase (SHP2), we demonstrate that the functional inter-domain motion is observationally non-ergodic over the time spans 10-12 to 10-7 s and 10-1 to 102 s. The difference between observational non-ergodicity and simple non-convergence is discussed. In comparison, a single-strand DNA of similar size behaves ergodically with an energy landscape resembling a one-dimensional linear chain. The observed non-ergodicity results from the hierarchical connectivity of the high-dimensional energy landscape of the protein molecule. As the characteristic time for the protein to conduct its dephosphorylation function is ∼10 s, our findings suggest that, due to the non-ergodicity, individual, seemingly identical protein molecules can be dynamically and functionally different.