Request for Free Energy Integration Files Using Dummy Atoms

User discussions
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GROMACS version: 2021.2
GROMACS modification: No
Hello everyone,
I’m looking for some assistance with relative free energy integration using dummy atoms. If anyone could share .itp and .mdp files that they’ve successfully used for this purpose, it would be a great help. Additionally, if you have a forcefield.itp that details the interactions of the dummy atoms, that would also be beneficial.

I already did it using the following itp and mdp files (here I put only the production step):
NC9toNC5_itpfile.top (20.1 KB)
md.mdp (3.6 KB)

However, the result is far from the result of substraction of two solvation free energy of those ligands (using ‘couple-intramol = no’).
To keep it brief, it would be really useful if someone could provide an example of an .itp file that works correctly using dummy atoms. I’ve found some .mdp files online but not an appropriate .itp file.

Thanks in advance,
My mail is: yehon.levy@mail.huji.ac.il

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Hi, the pmx webserver is a great tool for creating alchemical topologies for free energy calculations. For most mutations it creates a full “dual topology”, but if I remember correctly, purine-purine or pyrimidine-pyrimidine mutations in DNA follow the “single topology” approach too. You can then use the outputs to get familiar with the format.

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Thank you for the insight. I looked at the files on the PMX website. My problem actually was that I removed the Coulomb and van der Waals interactions together, not separately.

I would like to ask another question. I started to write the script for the merged topology by myself; however, I prefer to use something built-in. Can I get advise please on the most commonly used and simplest methods to do this in GROMACS? (I’m using CGenFF and simulating graft carbon chain ligands.)

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It really depends, I remember e.g. there was this tool for finding common substructures and making them into alchemical topologies, and perhaps a few more, but I never tested them myself.

For simple but routine modifications, or perhaps to build a custom workflow while avoiding re-implementing all the topology-related nuisances, I added a few simple routines in my own library, nothing too general though. If needed, I can always consider adding some simple functions.