  We investigate the effects of solvent specificities on the stability of the
native structure (NS) of a protein on the basis of our free-energy function
(FEF). We use CPB-bromodomain (CBP-BD) and apoplastocyanin (apoPC) as
representatives of the protein universe and water, methanol, ethanol, and
cyclohexane as solvents. The NSs of CBP-BD and apoPC consist of 66$\%$
$\alpha$-helices and of 35$\%$ $\beta$-sheets and 4$\%$ $\alpha$-helices,
respectively. In order to assess the structural stability of a given protein
immersed in each solvent, we contrast the FEF of its NS against that of a
number of artificially created, misfolded decoys possessing the same amino-acid
sequence but significantly different topology and $\alpha$-helix and
$\beta$-sheet contents. We find that for both CBP-BD and apoPC, the energetic
component dominates in methanol, ethanol, and cyclohexane, with the most stable
structures in these solvents sharing the same characteristics described as an
association of a-helices. In water, the entropic component is as strong as or
even stronger than the energetic one, with a large gain of translational,
configurational entropy of water becoming crucially important, so that the
relative contents of $\alpha$-helix and $\beta$-sheet and the content of total
secondary structures are carefully selected to achieve sufficiently close
packing of side chains. Our analysis, which requires minimal computational
effort, can be applied to any protein immersed in any solvent and provides
robust predictions that are quite consistent with the experimental observations
for proteins in different solvent environments, thus paving the way toward a
more detailed understanding of the folding process.
