The Role of Bonded Terms in Free Energy Simulations. 2. Calculation of Their Influence on Free Energy Differences of Solvation

Calculations of the free energy difference of solvation are used to study the contributions arising from alchemical changes of bond stretching and angle bending energy terms in the force field. The results illustrate the theoretical analysis of such terms given in the companion paper (Boresch, S.; Karplus, M. The Role of Bonded Terms in Free Energy Simulations:  1. Theoretical Analysis. J. Phys. Chem. A 1998, 103, 10310). Three model systems are investigated:  (a) two one-dimensional harmonic oscillators interacting with a third particle that represents the solvent, (b) the aqueous solvation of two diatomic molecules, and (c) the aqueous solvation of ethane and methanol. In each case, the computations are carried out with both a single topology and a dual topology methodology. A comparison of free energy components of the single and double free energy differences obtained in the calculations makes it possible to identify the three contributions that the theoretical analysis showed were involved, i.e., vib...