Direct measurement of protein energy landscape roughness

The energy landscape of proteins is thought to have an intricate, corrugated structure. Such roughness should have important consequences on the folding and binding kinetics of proteins, as well as on their equilibrium fluctuations. So far, no direct measurement of protein energy landscape roughness has been made. Here, we combined a recent theory with single‐molecule dynamic force spectroscopy experiments to extract the overall energy scale of roughness ε for a complex consisting of the small GTPase Ran and the nuclear transport receptor importin‐β. The results gave ε>5kBT, indicating a bumpy energy surface, which is consistent with the ability of importin‐β to accommodate multiple conformations and to interact with different, structurally distinct ligands.

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