Progressive stabilization of intermediate and transition states in proteinfolding reactions by introducing surface hydrophobic residues

It can be argued from the principle of solvent exclusion that the introduct ion of hydrophobic residues onto the surface of a protein wildrophobic surf ace mutations. This effect is slightly moderated in the folded state presum ably by the perturbation of van der Waals' contacl not destabilize the fold ed state because the nonpolar side chain will be at least as exposed in oca l electrostatic interactions that have a greater influence in this fully co mpact structure. The fact that in all but one case we find that stabilizati on of the rapidly collapsthe unfolded state as it is when the protein chain is folded. A comparison of the folding pathway of wild type and 11 site-di rected mutants of CD2.d1 shows this to be true. In fact, owing to partial b urial of nonpolar groups as folding proceeds, we find that the rapidly form ed intermediate state and, to a greater extent, the transition state are ge nerally stabilized by hyts and/or led intermediate is accompanied by a fast er acquisition of the folded state refutes the argument that I states are g enerally "off pathway" conformations or ensembles that lead to the inhibiti on of otherwise more rapid folding trajectories.