[gmx-users] FEP in vacuum simulation - inconsistent results among FEP methods

Melania T melaniacompchem at gmail.com
Wed May 29 01:30:00 CEST 2019

I am calculating the free energy change in transforming one small molecule
into another by the simple removal of a CO2 from the first molecule, and
also mutating some bond parameters slighty since the second molecule has a
couple different atom types in GAFF without the CO2 attached to it.

I analyze the results using alchemical_analysis.py

In solution, the change in free energy is consistent among all 6 default
methods used in alchemical_analysis.py (TI, TI-cubic, DEXP, IEXP, BAR,

However in vacuum after 100 ns, the results are still very different among
the methods. I use 10 coulomb windows and 20 LJ/Bond windows for both
simulations (evenly spaced). According to the dF_t plot printed by
alchemical_analysis.py the results are converged for MBAR for pretty much
the entire simulation. Gromacs/2019.1

(units in kJ/mol)

TI : 0.284 +/- 0.014
TI-CUBIC: 1.483 +/- 0.015
DEXP: -7.196 +/- 0.016
IEXP: -7.290 +/- 0.014
BAR: -7.236 +/- 0.009
MBAR: -6.110 +/- 0.008

Is this common in vacuum simulations or am I likely doing something wrong?

is it normal to have to use more lambda windows in a vacuum simulation than
in solution?



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