A new method for predicting binding free energy between receptor and ligand.
A practical method to estimate binding free energy, deltaG(bind), of a given ligand structure to the target receptor has been developed. The method assumes that deltaG(bind) is given by the summation of intermolecular interaction energy, deltaG(inter), and partial desolvation energy, deltaG(desolv). DeltaG(desolv) is calculated from the buried surface area in the complex between the ligand and receptor, based on solvation energy, deltaG(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 deltaG(inter) and each term of deltaG(desolv) using observed deltaG(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 deltaG(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.
Takamatsu
Y
Y
Faculty of Pharmaceutical Sciences, The University of Tokyo, Japan.
Itai
A
A
D000818:Animals; D001360:Avidin / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004735:Energy Transfer; D029968:Escherichia coli Proteins; D008024:Ligands; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*
C016242:AraF protein, E coli; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008024:Ligands; D001360:Avidin; D013762:Tetrahydrofolate Dehydrogenase