Calculated solvation free energies of amino acids in a dipolar approximation

The solvation foe energies of amino acids (hydrophobicities) are rationalized here by using a simple electrostatic ab initio model. The parameters of the model are the surface energy density (gamma = 9.55 kJ/mol/nm(2), the same for all atoms), the fractional charges, and the radii of the atoms of the amino acids. From the fractional charges, dipoles are constructed, and the polarization energies (self-energies) of the dipoles are calculated. The saturation effect of the solvent is included in the model. The dipole electrostatic contribution is in general not very sensitive to the choice of parameters. In contrast, the self-energies of single net charges are extremely sensitive to the choice of the Born radius. However, for amino acids that may carry a net charge, this energy will be prohibitively large in a low-dielectric medium. Therefore, they will in general change their protonation state to become neutral. The energetic cost of this is calculated from the difference between the amino acid side chain pK(a)'s and the pH of the solvent. This results in a hydrophobicity scale for amino acid side chains based on fundamental physics that agrees well with experimental hydrophobicity scales. The solvation energy for the amino acid backbone (the peptide bond) can also be calculated in this way. This gives good agreement with available experimental data.