A desolvation barrier to hydrophobic cluster formation may contribute to the rate-limiting step in protein folding

TitleA desolvation barrier to hydrophobic cluster formation may contribute to the rate-limiting step in protein folding
Publication TypeJournal Article
Year of Publication1997
AuthorsRank, J. A., & Baker D.
JournalProtein science
Volume6
Issue2
Pagination347-54
Date Published1997 Feb
ISSN0961-8368
KeywordsKinetics, Monte Carlo Method, Primary Publication, Protein Folding, Water
Abstract

To gain insight into the free energy changes accompanying protein hydrophobic core formation, we have used computer simulations to study the formation of small clusters of nonpolar solutes in water. A barrier to association is observed at the largest solute separation that does not allow substantial solvent penetration. The barrier reflects an effective increase in the size of the cavity occupied by the expanded but water-excluding cluster relative to both the close-packed cluster and the fully solvated separated solutes; a similar effect may contribute to the barrier to protein folding/unfolding. Importantly for the simulation of protein folding without explicit solvent, we find that the interactions between nonpolar solutes of varying size and number can be approximated by a linear function of the molecular surface, but not the solvent-accessible surface of the solutes. Comparison of the free energy of cluster formation to that of dimer formation suggests that the assumption of pair additivity implicit in current protein database derived potentials may be in error.

Alternate JournalProtein Sci.
AttachmentSize
rank97A.pdf1.76 MB