Example calculation of the difference in free energy of hydration upon transforming methane into tetrafluoromethane with LAMMPS using compute fep, fix adapt/fep and pair lj/cut/coul/long/soft.

Methane and tetrafluoromethane are represented by the OPLS-AA force field (1 molecule). Water is represented by the 3-site SPC/E model (360 molecules).

The procedure used to perform the alchemical transformation is the following:

The dual topology approach is used, therefore all the atoms of methane and perfluorommethane are present throughout the simulation, only some of them are dummy sites at the endpoints of the transformation. Masses and intramolecular terms (bonds, angles, dihedrals) are not changed.
Interactions of sites that are being created (from dummy sites, XD-) or deleted (to become dummy sites X-D) are treated using soft-core versions of the Lennard-Jones and Coulomb potentials (pair lj/cut/coul/long/soft) in order to avoid singularities. The exponent of the coupling parameter lambda in the soft-core pair potentials was in this example n = 1.
Atoms of the fragments being created should not interact with atoms being deleted. In this small solute this is guaranteed by the exclusion of 1-2 and 1-3 interactions, so no modifications of the pair_coeff are needed. Otherwise the LJ epsilon of those interactions should be zeroed.
Eletrostatic charges that are modified are varied linearly from the initial to the final values. This keeps the overall charge of the molecule constant, which is good for the long range electrostatics (the coupling parameter lambda has no effect on the kspace terms).

The following directories contain input files and results for calculations using the free-energy perturbation and Bennet's acceptance ratio (BAR) method:

mols -- molecule description files and force field database used to create the initial configurations used for the simulations data.0.lmp and data.1.lmp
fep01 -- Calculation using FEP, 20-step transformation of a CH4 molecule into CF4, constant NpT. Results in fep01.fep
fep10 -- Calculation using FEP, 20-step transformation of a CF4 molecule into CH4, constant NpT. Results in fep10.fep
bar01 -- Calculation using BAR, 1-step transformation of a CH4 molecule into CF4, constant NVT, Results in bar01.fep
bar10 -- Calculation using BAR, 1-step transformation of a CF4 molecule into CH4, constant NVT. Results in bar10.fep

The Python scripts fep.py and bar.py found in the tools directory can be used to calculate the free-energy difference corresponding to the transformation:

fep.py 300 < fep01.fep

fep.py 300 < fep10.fep

bar.py 300 bar01.lmp bar10.lmp

The outputs are in kcal/mol and can be compared with the experimental value of 1.2 kcal/mol, and also with a simulation value from the literature using a different force field): 0.8 kcal/mol Gough, Pearlman, Kolmann, J Chem Phys 99 (1993) 9103. This is a small free energy difference so consider the absolute discrepancies.

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.)