LAUSR

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.