Solvation Free Energies of Amino Acids Calculated by Molecular Dynamics/Free Energy Perturbation Method.

Abstract

It has been accepted that free energy differences between amino acids calculated using computer simulations are in good agreement with the corresponding experimental values. In recent years, however, Sharp et al. [Biochemistry, 30, 9686 (1991)] pointed out that the experimental solvation free energies had been underestimated and suggested reevaluation of the extent of agreement between the experiment and computer simulations. We calculated the free energy differences of transfer from vapor to water between neutral amino acids using molecular dynamics/free energy perturbation method and compared the calculated values (ΔΔGcalc) with both the uncorrected values (ΔΔGuncorr) obtained by Wolfenden et al. [Science, 206, 575 (1979); Biochemistry, 20, 849 (1981)] and the corrected values (ΔΔGcorr) by Sharp et al. considering the effect of solute-solvent size differences. For the uncorrected values, the correlation coefficient was r=0.938 and the simple regression equation was ΔΔGuncorr=0.823ΔΔGcalc-0.235. For the corrected values, the correlation coefficient and the simple regression equation were r=0.987 and ΔΔGcorr=1.042ΔΔGcalc-0.172, respectively. It was shown that the calculated values are in better agreement with the corrected values than with the uncorrected values.