  We study the solvation free energy of two different conformations (helix and
extended) of two different peptides (deca-alanine and deca-glycine) in two
different solvents (water and aqueous guanidinium chloride, GdmCl). The free
energies are obtained using the quasichemical organization of the potential
distribution theorem, an approach that naturally provides the repulsive
(solvophobic or cavity) and attractive (solvophilic) contributions to
solvation. The solvophilic contribution is further parsed into a chemistry
contribution arising from solute interaction with the solvent in the first
solvation shell and a long-range contribution arising from non-specific
interactions between the solute and the solvent beyond the first solvation
shell. The cavity contribution is obtained for two different envelopes,
$\Sigma_{SE}$ which theory identifies as the solvent excluded volume and a
larger envelope ($\Sigma_G$) beyond which solute-solvent interactions are
Gaussian. For both envelopes, the cavity contribution in water is proportional
to the surface area of the envelope. The same does not hold for GdmCl(aq),
revealing limitations of using molecular area to assess solvation energetics,
especially in mixed solvents. The $\Sigma_G$-cavity contribution predicts that
GdmCl(aq) should favor the more compact state, contrary to the role of GdmCl in
unfolding proteins. The chemistry contribution attenuates this effect, but
still the net local (chemistry plus $\Sigma_G$-packing) contribution is
inadequate in capturing the role of GdmCl. With the inclusion of the long-range
contribution, which is dominated by van~der~Waals interaction, aqueous GdmCl
favors the extended conformation over the compact conformation. Our finding
emphasizes the importance of weak, but attractive, long-range dispersion
interactions in protein solution thermodynamics.
