  Using thermodynamics integration, we study the solvation free energy of 18
amino acid side chain equivalents in solvents with different polarity, ranging
from the most polar water to the most non-polar cyclohexane. The amino acid
side chain equivalents are obtained from the 20 natural amino acids by
replacing the backbone part with a hydrogen atom, and discarding proline and
glycine that have special properties. A detailed analysis of the relative
solvation free energies suggests how it is possible to achieve a robust and
unambiguous hydrophobic scale for the amino acids. By discriminating the
relative contributions of the entropic and enthalpic terms, we find strong
negative correlations in water and ethanol, associated with the well-known
entropy-enthalpy compensation, and a much reduced correlation in cyclohexane.
This shows that in general the role of the polar and non-polar moieties cannot
be reversed in a non-polar solvent. Our findings are compared with past
experimental as well as numerical results, and may shed additional light on the
unique role of water as biological solvent.
