Solvation Energy Contributions to Binding Energies

Abstract

Binding affinities for the association of protein chains, and for the association of a drug to DNA, are examined with atomic salvation parameters (ASPs). ASPs permit an estimate of the solvation free energy of binding in aqueous solution, starting from known atomic coordinates. ASPs are semiempirical coefficients, giving the free energy change per unit surface area for the transfer of each type of chemical group from a relatively apolar environment, such as the interior of a protein, to the aqueous surface. For this estimate of free energy, the accessible surface area of an atomic group is computed, first for the free ligand and macromolecule, and then for the complex. The change in surface area is multiplied by the ASP for the group and summed with terms for all other groups to give the standard free energy change. Tests of the procedure are described for: (a) The tetramerization of melittin; (b) The formation of a DNA-drug complex; (c) The polymerization of tobacco mosaic protein subunits; and (d) The rotational isomerization of butane.