SOLVATION FREE-ENERGIES OF AMINO-ACIDS CALCULATED BY MOLECULAR-DYNAMICS FREE-ENERGY PERTURBATION METHOD

It has been accepted that free energy differences between amino acids calculated using computer simulations are in good agreement with the c orresponding experimental values, In recent years, however, Sharp et a l, [Biochemistry, 30, 9686 (1991)] pointed out that the experimental s olvation free energies had been underestimated and suggested reevaluat ion of the extent of agreement between the experiment and computer sim ulations, We calculated the free energy differences of transfer from v apor to water between neutral amino acids using molecular dynamics/fre e energy perturbation method and compared the calculated values (Delta Delta G(calc)) with both the uncorrected values (Delta Delta G(uncorr )) obtained by Wolfenden et al, [Science, 206, 575 (1979); Biochemistr y, 20, 849 (1981)] and the corrected values (Delta Delta G(corr)) by S harp et al, considering the effect of solute-solvent size differences, For the uncorrected values, the correlation coefficient was r=0.938 a nd the simple regression equation was Delta Delta G(uncorr)=0.823 Delt a Delta G(calc)-0.235, For the corrected values, the correlation coeff icient and the simple regression equation were r=0.987 and Delta Delta G(corr)=1.042 Delta Delta G(calc)-0.172, respectively, It was shown t hat the calculated values are in better agreement with the corrected v alues than with the uncorrected values.