Use of thermodynamic integration to calculate the hydration free energies of n-alkanes

Abstract

Explicit atom molecular dynamics simulations were used in conjunction with the thermodynamic integration method to calculate hydration free energies for short n-alkane molecules, up to C5H12. The OPLS all-atom parameter set [Kaminski et al., J. Phys. Chem. 98, 13077 (1994)] was used to represent the n-alkanes, together with the TIP3P water model [Jorgensen et al., J. Chem. Phys. 79, 926 (1983)]. The approach of Beutler et al. [Chem. Phys. Lett. 222, 529 (1994)] was used to avoid singularities in nonbonded interaction potentials that can otherwise be problematical with this technique. Electrostatic interactions were treated using a cutoff radius of 0.9 nm, and a functional form that was shifted and scaled smoothly to zero. The values obtained for the solvation free energies were of similar accuracy to those from previously published simulations, but were systematically about 2 kJ mol−1 higher than experimental values. However, the calculated free energies of transformation for the reaction CnH2n+1(aq)→Cn+1H2n+4(aq), show a considerably improved agreement over previous values, and reproduce well the experimental trend versus n. The merits of the thermodynamic integration technique are discussed in relation to the popular thermodynamic perturbation method.