  To better understand protein-solvent interaction we have analyzed a variety
of physical and geometrical properties of the solvent-excluded surfaces (SESs)
over a large set of soluble proteins with crystal structures. We discover that
all have net negative surface charges and permanent electric dipoles. Moreover
both SES area and surface charge as well as several physical and geometrical
properties defined by them change with protein size via well-fitted power laws.
The relevance to protein-solvent interaction of these physical and geometrical
properties is supported by strong correlations between them and known
hydrophobicity scales and by their large changes upon protein unfolding. The
universal existence of negative surface charge and dipole, the characteristic
surface geometry and power laws reveal fundamental but distinct roles of
surface charge and SES in protein-solvent interaction and make it possible to
describe solvation and hydrophobic effect using theories on anion solute in
protic solvent. In particular the great significance of surface charge for
protein-solvent interaction suggests that a change of perception may be needed
since from solvation perspective folding into a native state is to optimize
surface negative charge rather than to minimize the hydrophobic surface area.
