V. S. Pande. Physical Review Letters (2010).
SUMMARY.
Recent work from detailed simulations of protein folding resulting from Folding@home have suggested some surprises and radical changes in how one conceptualizes protein folding kinetics. One of the more unusual aspects found in these simulations is the role of the native state as a kinetic hub (see paper #74). Here, we propose a new theory of protein folding that uses structural information in its kinetic equations and gives a much richer picture than previous theories. One key result is a prediction for what would cause the native state to be a kinetic hub and when one would see this effect (and in particular why it was not seen in simpler simulation studies previously).
ABSTRACT.
We present a simple model of protein folding dynamics that captures key qualitative elements recently seen in all-atom simulations. The goals of this theory are to serve as a simple formalism for gaining deeper insight into the physical properties seen in detailed simulations as well as to serve as a model to easily compare why these simulations suggest a different kinetic mechanism than previous simple models. Specifically, we find that non-native contacts play a key role in determining the mechanism, which can shift dramatically as the energetic strength of non-native interactions is changed. For protein-like non-native interactions, our model finds that the native state is a kinetic hub, connecting the strength of relevant interactions directly to the nature of folding kinetics.