Living in a world without barriers: Analysis of downhill protein folding


Victor Muņoz,, Center for Biological Investigations, Spanish Research Council - University of Maryland, Ramiro de Maeztu 9, Madrid, Spain
Protein folding has been commonly characterized as a simple all or none process in which protein molecules interconvert between two states: unfolded and native, which are separated by a high free energy barrier. Recent progress in the field has led to the realization that folding barriers are much smaller than previously thought and to the identification of examples of folding over marginal or no barriers (downhill folding). The discovery of downhill folding opens a new avenue of experimental research in which it may be feasible to characterize the whole unfolding process with atomic resolution, measure conformational dynamics during folding, and resolve entire folding trajectories on single molecules. In parallel, experimental studies on downhill protein folding challenge many of the assumptions that have been conventionally made in the analysis of protein folding experiments. In this lecture I will review some of the peculiarities of downhill folding and present new experimental progress towards defeating the three resolution limits (structural, temporal, and statistical) in protein folding.