Single-molecule force spectroscopy reveals signatures of glassy dynamics in the energy landscape of ubiquitin

The conformational energy landscape of a protein out of equilibrium is poorly understood. We use single-molecule force-clamp spectroscopy to measure the kinetics of unfolding of the protein ubiquitin under a constant force. We discover a surprisingly broad distribution of unfolding rates that follows a power law with no characteristic mean. The structural fluctuations that give rise to this distribution reveal the architecture of the protein's energy landscape. Following models of glassy dynamics, this complex kinetics implies large fluctuations in the energies of the folded protein, characterized by an exponential distribution with a width of 5-10k(B)T. Our results predict the existence of a 'glass transition' force below which the folded conformations interconvert between local minima on multiple timescales. These techniques offer a new tool to further test statistical energy landscape theories experimentally.