ABSRTACT
A practical method to estimate binding free energy, ⌬ ⌬ ⌬ ⌬G bind , of a given ligand structure to the target receptor has been developed. The method assumes that ⌬ ⌬ ⌬ ⌬G bind is given by the summation of intermolecular interaction energy, ⌬ ⌬ ⌬ ⌬G inter , and partial desolvation energy, ⌬ ⌬ ⌬ ⌬G desolv . ⌬ ⌬ ⌬ ⌬G desolv is calculated from the buried surface area in the complex between the ligand and receptor, based on solvation energy, ⌬ ⌬ ⌬ ⌬G solv , formulated by an equation which can be calibrated with observed values. Then, the method was applied to arabinose-binding protein (ABP) and dihydrofolate reductase (DHFR), after recalibrating the weights for ⌬ ⌬ ⌬ ⌬G inter and each term of ⌬ ⌬ ⌬ ⌬G desolv using observed ⌬ ⌬ ⌬ ⌬G bind data for 29 known ligands to avidin (AV). The usefulness of our method was confirmed by the fact that correlation coefficients between the calculated and observed ⌬ ⌬ ⌬ ⌬G bind' s in AV, ABP and DHFR were 0.92, 0.77, and 0.88, whereas the corresponding values obtained by simple force field calculation were 0.79, 0.30, and 0.79, respectively. Further investigations to improve the method and validate the parameters are in progress. Pro-