Robustness of protein folding kinetics to surface hydrophobic substitutions

We use both combinatorial and site-directed mutagenesis to explore the cons equences of surface hydrophobic substitutions for the folding of two small single domain proteins, the are SH3 domain, and the IgG binding domain of P eptostreptococcal protein L. We find that in almost every case, destabilizi ng surface hydrophobic substitutions have much larger effects on the rate o f unfolding than on the rate of folding, suggesting that nonnative hydropho bic interactions do not significantly interfere with the rate of core assem bly.