  The interplay between structure-search of the native structure and
desolvation in protein folding has been explored using a minimalist model.
These results support a folding mechanism where most of the structural
formation of the protein is achieved before water is expelled from the
hydrophobic core. This view integrates water expulsion effects into the funnel
energy landscape theory of protein folding. Comparisons to experimental results
are shown for the SH3 protein. After the folding transition, a near-native
intermediate with partially solvated hydrophobic core is found. This transition
is followed by a final step that cooperatively squeezes out water molecules
from the partially hydrated protein core.
