DENATURANTS CAN ACCELERATE FOLDING RATES IN A CLASS OF GLOBULAR-PROTEINS

We present a lattice Monte Carlo study to examine the effect of denatu rants on the folding rates of simplified models of proteins. The two-d imensional model is made from a three-letter code mimicking the presen ce of hydrophobic, hydrophilic, and cysteine residues. We show that th e rate of folding is maximum when the effective hydrophobic interactio n epsilon(H) is approximately equal to the free energy gain epsilon(s) upon forming disulfide bonds. In the range 1 less than or equal to ep silon(H)/epsilon(S) less than or equal to 3, multiple paths that conne ct several intermediates to the native state lead to fast folding. It is shown that at a fixed temperature and epsilon(S) the folding rate i ncreases as epsilon(H) decreases. An approximate model is used to show that epsilon(H) should decrease as a function of the concentration of denaturants such as urea or guanidine hydrochloride. Our simulation r esults, in conjunction with this model, are used to show that increasi ng the concentration of denaturants can lead to an increase in folding rates. This occurs because denaturants can destabilize the intermedia tes without significantly altering the energy of the native can format ion. Our findings are compared with experiments on the effects of dena turants on the refolding of bovine pancreatic trypsin inhibitor and ri bonuclease T1. We also argue that the phenomenon of denaturant-enhance d folding of proteins should be general.