Methane is represented by the 5-site OPLS-AA model (1 molecule). Water is represented by the 4-site TIP4P-Ew model (360 molecules). Interactions of sites that are being created or deleted are treated using Lennard-Jones and Coulomb potentials with soft cores (pair lj/cut/coul/long/soft) in order to avoid singularities. Trajectories are at constant NpT, so corrections for the fluctuating volume are included.

The following directories contain input files and results for calculations using free-energy perturbation (FEP) and finite-difference thermodynamic integration (FDTI):

mols -- molecule description files and force field database used to create the initial configuration used for the simulations data.lmp
fep01 -- Calculation using FEP, multi-stage creation of a methane molecule. Results in fep01.fep
fep10 -- Calculation using FEP, multi-stage deletion of a methane molecule. Results in fep10.fep
fdti01 -- Calculation using TI/FDTI, creation of a methane molecule. Results in fdti01.fep
fdti10 -- Calculation using TI/FDTI, deletion a methane molecule. Results in fdti10.fep

The Python scripts fep.py, fdti.py and fti.py found in the tools directory can be used to calculate the free-energy differences corresponding to the transformations above:

fep.py 300 < fep01.fep

fep.py 300 < fep10.fep

fdti.py 300 0.002 < fdti01.fep

fdti.py 300 0.002 < fdti10.fep

nti.py 300 0.002 < fdti01.fep

nti.py 300 0.002 < fdti10.fep

The outputs are in kcal/mol and can be compared with the experimental value of 2.0 kcal/mol, or with a simulation value from the literature obtained with the same force field models used here: 2.27 kcal/mol MR Shirts, VS Pande, J Chem Phys 122 (2005) 134508.

These example calculations are for tutorial purposes only. The results may not be of research quality (not enough sampling, size of the step in lambda or of the delta for numerical derivative not optimized, no evaluation of ideal-gas contributions, etc.)