Prediction of Folding and Unfolding Rates of Proteins with Simple Models

Large differences exist between the experimentally measured folding and unfolding rates in single-domain proteins, which range from seconds to microseconds. Considerable effort has been dedicated to develop methods for the prediction of these rates using a simple set of rules. Much of this work has focused in identifying structural metrics derived from experimentally resolved protein structures that serve as good predictors of folding rates. An alternative to this ad-hoc methodology is the use of phenomenological free energy models, parametrized with empirical parameters. This alternative approach has become very useful to obtain estimates of folding and, importantly, also unfolding rates with only the information of protein size and secondary structure. Here we present the fundamentals of this type of approach and introduce a recent implementation of this predictive method.