Complex Dynamics in Single Molecule Force Spectroscopy from Simple Simulation Models

Abstract

Single molecule force spectroscopy studies of protein folding dynamics have yielded unprecedented insight into the mechanisms of the folding reaction. Still, they usually allow for a very limited description of the process of interest (e.g. based on the reaction coordinate that is probed directly). Molecular simulations --even using very simplified models-- can give a much enriched view of the underlying molecular events. In a recent example, we explain the observations on a prototypical two-state folding protein, the cold shock protein, that in the AFM turns out to exhibit multiple intermediate states. Using a very simple topology based model for the protein we show that in fact this should not come as a surprise. Indeed, force can selectively stabilize different protein intermediates and act in a very different way compared to that of chemical denaturants.