OpenFreeEnergy / OpenFreeEnergy/openfe

ABFE net charge support

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#2,001 0 comments 0 reactions 1 assignee View on GitHub

@IAlibay is already working on this.

Since Jun 15, 2026.

Dominant language
Python
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331
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Avg merge
3d 9h
Merged PRs (30d)
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Description

This is the overaching issue for adding net charge support in the OpenMM ABFE Protocol.

Net charge support will be added through the use of a co-alchemical ion that is annhilated alongside the ligand.

Some details:

  • In the first instance an ion of the opposite charge will be co-annhilated. We are aware of previous reports that this doesn't always close the thermodynamic cycle properly with lipids. However recent reports seem to indicate that this behaviour is not always seen. For ease of implementation, we will start with co-annhilation and then explore charge transfer once that is finished.
  • The transformation will be done with full nonbonded exclusions between the alchemical species, in a manner similar to SepTop. This should avoid some ligand-ion interaction issues as well as make it a lot easier to implement code-wise.

Contributor guide

Open the contributing guide

First steps

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  2. Comment on the issue to say you are picking it up — it saves two people doing the same work.
  3. Fork the repository and make your change on a branch.
  4. Open a pull request that references the issue number.

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