[gmx-users] Free Energy Change of Growing a Molecule

[Barnett, James W]

Good morning,


I'm looking at doing a free energy change with thermodynamic integration with GROMACS. Specifically I want to "grow" a molecule and find out the difference in the free energy. For example, I would like to see the free energy change between a methane and ethane.


I've looked at Dr. Lemkul's tutorial about free energy changes<http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/free_energy/index.html> and he refers to the manual regarding changing a molecule with a dual-toplogy approach. I've reviewed how to use two topologies in the manual in section 5.7.4. In the manual's example the number of atoms in the molecule remained the same from topology A to B.


My questions are:

  1.  Is it possible to calculate the free energy change as I am describing, where the number of atoms in the molecule changes from topology A to B?
  2.   If it is possible, how is this implemented in the dual topology approach?

I did find this thread<https://mailman-1.sys.kth.se/pipermail/gromacs.org_gmx-users/2005-May/015019.html> in the mailing list archive where someone basically answered "no", but the post is almost 10 years old and a few things have changed with GROMACS since then.


I'm thinking as an alternative, I could simply calculate the free energy change of adding a methane and the free energy change of adding an ethane. Then the free energy change of a methane changing into an ethane is simply the difference between the two.


Thanks for your help.


James Barnett

jbarnet4 at tulane.edu

Graduate Student

Chemical and Biomolecular Engineering

Tulane University