  Hydrophobicity is thought to be one of the primary forces driving the folding
of proteins. On average, hydrophobic residues occur preferentially in the core,
whereas polar residues tends to occur at the surface of a folded protein. By
analyzing the known protein structures, we quantify the degree to which the
hydrophobicity sequence of a protein correlates with its pattern of surface
exposure. We have assessed the statistical significance of this correlation for
several hydrophobicity scales in the literature, and find that the computed
correlations are significant but far from optimal. We show that this less than
optimal correlation arises primarily from the large degree of mutations that
naturally occurring proteins can tolerate. Lesser effects are due in part to
forces other than hydrophobicity and we quantify this by analyzing the surface
exposure distributions of all amino acids. Lastly we show that our database
findings are consistent with those found from an off-lattice hydrophobic-polar
model of protein folding.
