Interatomic potentials and solvation parameters from protein engineering data for buried residues.

Van der Waals (vdW) interaction energies between different atom types, energies of hydrogen bonds (H-bonds), and atomic solvation parameters (ASPs) have been derived from the published thermodynamic stabilities of 106 mutants with available crystal structures by use of an originally designed model for the calculation of free-energy differences. The set of mutants included substitutions of uncharged, inflexible, water-inaccessible residues in alpha-helices and beta-sheets of T4, human, and hen lysozymes and HI ribonuclease. The determined energies of vdW interactions and H-bonds were smaller than in molecular mechanics and followed the "like dissolves like" rule, as expected in condensed media but not in vacuum. The depths of modified Lennard-Jones potentials were -0.34, -0.12, and -0.06 kcal/mole for similar atom types (polar-polar, aromatic-aromatic, and aliphatic-aliphatic interactions, respectively) and -0.10, -0.08, -0.06, -0.02, and nearly 0 kcal/mole for different types (sulfur-polar, sulfur-aromatic, sulfur-aliphatic, aliphatic-aromatic, and carbon-polar, respectively), whereas the depths of H-bond potentials were -1.5 to -1.8 kcal/mole. The obtained solvation parameters, that is, transfer energies from water to the protein interior, were 19, 7, -1, -21, and -66 cal/moleA(2) for aliphatic carbon, aromatic carbon, sulfur, nitrogen, and oxygen, respectively, which is close to the cyclohexane scale for aliphatic and aromatic groups but intermediate between octanol and cyclohexane for others. An analysis of additional replacements at the water-protein interface indicates that vdW interactions between protein atoms are reduced when they occur across water.