title: Single-molecule unfolding force distributions reveal a funnel-shaped energy landscape.
abstract: The protein folding process is described as diffusion on a high-dimensional energy landscape. Experimental data showing details of the underlying energy surface are essential to understanding folding. So far in single-molecule mechanical unfolding experiments a simplified model assuming a force-independent transition state has been used to extract such information. Here we show that this so-called Bell model, although fitting well to force velocity data, fails to reproduce full unfolding force distributions. We show that by applying Kramers' diffusion model, we were able to reconstruct a detailed funnel-like curvature of the underlying energy landscape and establish full agreement with the data. We demonstrate that obtaining spatially resolved details of the unfolding energy landscape from mechanical single-molecule protein unfolding experiments requires models that go beyond the Bell model.
authors.forename: Michael
authors.initials: M
authors.lastname: Schlierf
authors.forename: Matthias
authors.initials: M
authors.lastname: Rief
mesh_terms: D008958:Models, Molecular; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins