1. Large changes in AA. sequence, either experimental or evolutionary, that don't alter the overall topology of a protein usually have less than tenfold effect on the rate of protein folding.

This suggests evolution has not optimized protein sequences for rapid folding, an encouraging result for simple model development.

2. Using the consequences of mutations on folding kinetics to probe the transition states of proteins with similar structures but very different sequences has shown that the structures of these transition states are relatively insensitive to large-scale changes in sequence.

For example in Box 1 there are two examples of pairs of structurally related proteins with little or no sequence similarity that have very similar folding transition-state ensembles.

3. The folding rates of small proteins correlate with a property of the native state topology: the average sequence separation between residues that make contacts in the three-dimensional structure (the 'contact order'; Box 1).

This correlation holds over a million-fold range of folding rates, and is remarkable given the large differences in the sequences and structures of the proteins compared. Simple geometrical considerations appear to explain much of the difference in the folding rates of different proteins.