[ WIP ] Membrane support #1561

hannahbaumann · 2025-10-09T14:40:19Z

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codecov · 2025-10-10T10:13:38Z

Codecov Report

❌ Patch coverage is 98.55491% with 5 lines in your changes missing coverage. Please review.
✅ Project coverage is 93.23%. Comparing base (3d65447) to head (683b47d).

Files with missing lines	Patch %	Lines
openfe/protocols/openmm_md/plain_md_methods.py	80.00%	2 Missing ⚠️
openfe/protocols/openmm_utils/system_validation.py	81.81%	2 Missing ⚠️
...nfe/protocols/openmm_septop/equil_septop_method.py	93.33%	1 Missing ⚠️

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@@            Coverage Diff             @@
##             main    #1561      +/-   ##
==========================================
- Coverage   95.39%   93.23%   -2.17%     
==========================================
  Files         189      189              
  Lines       16646    16922     +276     
==========================================
- Hits        15880    15777     -103     
- Misses        766     1145     +379

Flag	Coverage Δ
fast-tests	`93.23% <98.55%> (?)`
slow-tests	`?`

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IAlibay

Some quick things for now.

openfe/protocols/openmm_afe/equil_binding_afe_method.py

IAlibay · 2026-01-13T17:08:40Z

openfe/protocols/openmm_afe/equil_binding_afe_method.py

+
+        # If there is an SolvatedPDBComponent, we set the solv_comp
+        # in the complex to None, as it is only used in the solvent leg
+        if isinstance(prot_comp, SolvatedPDBComponent):


Why not just return that component? That way we can still assert that solv_comp == None means that there is no solvent.

I think I'm not quite following you what you mean here. As we are returning the SolvatedPDBComponent in the prot_comp, are you suggesting to also return it in the solv_comp , in addition or instead of the "normal" SolventComponent? In the membrane case you would currently have both, the SolvatedPDBComponent and the SolventComponent in the ChemicalSystem, one for the complex and one for the solvent.

IAlibay · 2026-01-13T17:10:28Z

src/openfe/protocols/openmm_utils/omm_settings.py

    barostat_frequency: TimestepQuantity = 25.0 * unit.timestep
    """
    Frequency at which volume scaling changes should be attempted.
    Note: The barostat frequency is ignored for gas-phase simulations.
    Default 25 * unit.timestep.
    """
+    surface_tension: Optional[SurfaceTensionQuantity] = 0 * unit.bar * unit.nanometer


Maybe add a validator that this shouldn't be non-zero if you aren't using a MonteCarloBarostat?

I added a validator ensuring the surface_tension is not None when the MonteCarloMembraneBarostat is present. Should there also be a validator to check that the surface_tension is either None or zero when the MonteCarloBarostat is present?

Yeah, I think that would be useful - at least users should know that value doesn't do anything in that case.

IAlibay · 2026-01-13T17:14:13Z

openfe/protocols/openmm_utils/system_validation.py

    solv_comps = state.get_components_of_type(SolventComponent)
+    base_solv_comps = state.get_components_of_type(BaseSolventComponent)


Just do the second one and then do an isinstance check later.

I attempted a rewrite of this function, however I'm not sure if this is more clear. The challenge is that the ChemicalSystems for these membrane systems are a bit confusing since they will have the SolvatedPDBComponent for the complex leg and a SolventComponent for the solvent leg.
So I think what we're currently supporting is:

Vacuum (no BaseSolventComponent)

One SolventComponent

One SolventComponent paired with one SolvatedPDBComponent

Or would we want to support more scenarios at the moment?

IAlibay · 2026-01-13T17:14:26Z

openfe/protocols/openmm_utils/system_validation.py

            raise ValueError(errmsg)

-        if solv_comps[0].smiles != "O":
+        if len(solv_comps) == 1 and solv_comps[0].smiles != "O":


Do the isinstance check here.

IAlibay · 2026-01-13T17:15:57Z

openfe/protocols/openmm_utils/system_validation.py

            errmsg = "nocutoff cannot be used for solvent transformations"
            raise ValueError(errmsg)

        if len(solv_comps) > 1:


We either should error out if we have more than one solvated PDB component too, or we need to change this so that you have the isinstance check that covers the below test too and then a separate check that if it's a solvated PDB component the box vectors have to be the same across all the PDBs.

For now we only allow for one protein component, so maybe just enforce that here too?

Technically we're already enforcing that in the validate_protein, since the SolvatedPDBComponent is also a ProteinComponent it should error out in that check as well. Or do you think we should doublecheck that here as well?
This means of course that we're currently not supporting the presence of one "normal" ProteinComponent and one SolvatedPDBComponent at the same time.

openfe/tests/protocols/openmm_abfe/test_abfe_protocol.py

openfe/tests/protocols/openmm_rfe/test_hybrid_top_protocol.py

Co-authored-by: Irfan Alibay <IAlibay@users.noreply.github.com>

hannahbaumann · 2026-01-15T09:33:13Z

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hannahbaumann · 2026-01-15T12:40:00Z

gather tests are failing as we will need to update result files on zenodo with the updated settings objects once we're settled on those.

github-actions · 2026-01-23T08:49:55Z

🚨 API breaking changes detected! 🚨
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hannahbaumann and others added 4 commits October 9, 2025 16:36

Membrane support prototype start

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Merge branch 'main' into membrane_prototype

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Point to corresponding branch in gufe

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Merge branch 'membrane_prototype' of https://github.com/OpenFreeEnerg…

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hannahbaumann and others added 25 commits October 13, 2025 13:41

Merge branch 'main' into membrane_prototype

b7c63d6

Make plain md protocol membrane ready

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Merge branch 'membrane_prototype' of https://github.com/OpenFreeEnerg…

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Merge branch 'main' into membrane_prototype

7fd5ca9

Dry run for membrane system for debugging

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Merge branch 'membrane_prototype' of https://github.com/OpenFreeEnerg…

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…y/openfe into membrane_prototype

Merge branch 'main' into membrane_prototype

238b36b

Merge branch 'main' into membrane_prototype

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Merge branch 'membrane_prototype' of https://github.com/OpenFreeEnerg…

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Add box vectors to modeller

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Adapt htf to allow for membrane barostat

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Fix test

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Add test files membrane

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Merge branch 'main' into membrane_prototype

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Change test to cpu

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Merge branch 'membrane_prototype' of https://github.com/OpenFreeEnerg…

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Merge branch 'main' into membrane_prototype

0cdde55

Prints for debugging

5bfd1c9

Some more debugginh stuff, remove later

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Merge branch 'main' into membrane_prototype

c53fd60

Small fix

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pre-commit-ci bot and others added 7 commits January 9, 2026 14:07

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ABFE enforce timestep complex solvent the same

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Merge branch 'main' into membrane_prototype

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Update test files

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IAlibay requested changes Jan 13, 2026

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hannahbaumann and others added 5 commits January 14, 2026 09:45

Update openfe/protocols/openmm_afe/equil_binding_afe_method.py

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Co-authored-by: Irfan Alibay <IAlibay@users.noreply.github.com>

Attempt at rewriting validate_solvent

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Move get barostat to self

e23d2a2

Simplify mapping in test

1936b83

Add validator for surface_tension and membrane barostat

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hannahbaumann requested a review from jthorton January 15, 2026 09:55

hannahbaumann added 2 commits January 15, 2026 11:09

Add membrane barostat to adaptive settings rfe protocol

a0a2ad1

Add validation/warning for barostat component mismatch

6a3a5a3

hannahbaumann linked an issue Jan 15, 2026 that may be closed by this pull request

Membrane: Add warning/validation for barostat usage #1790

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Fix tests (except CLI)

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hannahbaumann and others added 4 commits January 16, 2026 08:51

Address merge conflicts

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Merge branch 'main' into membrane_prototype

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hannahbaumann changed the title ~~[ WIP ] Membrane support prototype~~ [ WIP ] Membrane support Jan 19, 2026

Merge branch 'main' into membrane_prototype

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hannahbaumann requested a review from IAlibay January 22, 2026 09:46

Merge conflicts

5273d43

		solv_comps = state.get_components_of_type(SolventComponent)
		base_solv_comps = state.get_components_of_type(BaseSolventComponent)

[ WIP ] Membrane support #1561

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[ WIP ] Membrane support #1561

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