Tutorial for membrane RBFE calculation by hannahbaumann · Pull Request #286 · OpenFreeEnergy/ExampleNotebooks

hannahbaumann · 2026-02-06T13:54:00Z

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review-notebook-app · 2026-02-06T13:54:06Z

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github-actions · 2026-02-06T13:54:11Z

👈 Launch a Colab session on branch membrane_tutorial

jthorton · 2026-02-06T15:56:52Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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Line #25. settings=RelativeHybridTopologyProtocol._adaptive_settings(
Do we not need to add the lipid force field to the settings or is adaptive doing this? Also this is another place we are exposing _adaptive to the world do we need to add a public entry point?

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i currently added the lipid forcefields in the _adaptive_settings as well, but we can think about changing that later.

jthorton · 2026-02-06T15:56:52Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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Line #43. network = openfe.AlchemicalNetwork(transformations)
Woow so many warnings we need to remove a lot of these!

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Already done - Hannah's branch isn't up to date with main.

IAlibay · 2026-02-07T21:36:03Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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Two out of three of these imports warning seems to be some kind of problem with our typing vendor in gufe. I have opened an issue.

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IAlibay · 2026-02-07T21:36:03Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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For this example, rather than separating this in a separate step, I think it will be more useful to the readers if you just do these calls in-place, i.e. modeller = openmm.app.Modeller(protein.to_openmm_topology(), protein.to_openmm_positions().

With a little bit of formatting, that will look a lot less overwhelming.

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IAlibay · 2026-02-07T21:36:03Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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This is too unweidly for users in my opinion, I think OpenFreeEnergy/gufe#568 will need to be completed.

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That would be great!

IAlibay · 2026-02-07T21:36:03Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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Generally would not recommend overwriting an existing file in your example, that's going to lead users to do bad things on their end - I would instead suggest you set a new file name for it.

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db_complex = 'a2a/a2a_complex.pdb' is supposed to be a new file! I will remove it from the PR.

IAlibay · 2026-02-07T21:36:03Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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Could you somewhere make a statement about which of these would be applicable to the "merged PDB" example shown above? (give that most Maestro users would be going down that path).

numpy array using OpenFF units (see below)

This is the wrong level of details at this point, here I would just say "box vectors in OpenMM format". Then in the section below, I would precise that it has to be a united array.

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Added a maestro note and changed the box vector desciption.

openmm_rbfe/rbfe_membrane_protein.ipynb

IAlibay · 2026-02-07T21:36:03Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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Add some details on how this is done? Any caveats that one might need to consider (i.e. making sure that the system is wrapped / not broken across periodic images)?

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I added a comment on how it calculates the box and also a caveat.

IAlibay · 2026-02-07T21:36:03Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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Add some details on the types of lipid forcefields that are currently supported (i.e. I know there are some that won't work, which currently do work and which should one avoid?)

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Added a comment here. I haven't tried out ff other than lipid17, also commented on that.

jthorton · 2026-02-10T12:47:20Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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Do we need to say anything about how we expect the membrane to be aligned with the coordinate system so that the barostat applies the pressure correctly?

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Yes, added something!

ENH: it would be better if we move the "needs" to warning boxes and the likes. That way folks can easily see "o ok I have to be aware of this"

IAlibay · 2026-02-11T22:09:33Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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Following up from Monday's meeting - please remove the CHARMM36 bit here - we don't support non-AMBER force fields.

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Removed this!

jthorton · 2026-03-02T16:21:29Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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is this needed?

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This was just left from some trouble shooting, removed this.

jthorton · 2026-03-02T16:21:29Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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Should this be removed?

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Ah yeah, this was left over from some testing, removed this.

jthorton · 2026-03-02T16:25:30Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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This could be the entry point to OpenFE for some users so lets help them and guide them to the CLI docs for more info maybe to here https://docs.openfree.energy/en/latest/tutorials/rbfe_cli_tutorial.html#run-the-simulations ?

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jthorton

Just the two cells to remove and a link to the docs then please merge this looks great!

IAlibay

Can't merge as-is because the environment file is pointing to unreleased versions of openfe and gufe.

IAlibay · 2026-03-06T13:11:20Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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"It is essential that the lipid molecules include bond information in the CONECT records of the PDB file to ensure proper topology recognition by OpenMM."

This sentence seems to be a bit out of the blue and/or unexplained.

I.e.

Point 1: maestro does bad things, so you might need to save the different parts separately. -- makes sense!
Point 2: It's essential that you have all the CONECT records -- is this separate from the previous point? how do I achieve this as a Maestro user?
Point 3: you can merge the components this way (follows from point 1)

I would say either remove point 2, or make it clear how it's related or move it up and add a section higher up that goes "Reading in a PDB with a membrane" and then list the caveats there?

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IAlibay · 2026-03-06T13:11:20Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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[nit] the sentence technically reads as "OpenMM requires vectors numpy arrays with OpenFF units in their reduced form" (which they don't, just the latter).

I propose: "Box vectors must be provided as a NumPy array with OpenFF units. The vectors must be specified in their reduced form, as required by OpenMM."

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IAlibay · 2026-03-06T13:11:20Z

openmm_rbfe/rbfe_membrane_protein.ipynb

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The header level for validation seems to be too low. I think it should be the same size as the "loading" header font?

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IAlibay · 2026-03-06T13:12:02Z

The "notes" sections could be a little bit more visually striking if we used error and warning boxes. I'll open a PR targetting this one with some of these changes.

IAlibay · 2026-03-06T14:59:25Z

openmm_rbfe/rbfe_membrane_protein.ipynb

I just realised that this is the only tutorial under openmm_rbfe, which is a bit confusing because it's using the hybrid top protocol but RBFE could really mean septop (I know that's now how things are laid out inside of openfe, but that's also an issue in itself 😅 ).

How about moving it to just membranes for now?

Add tutorial for membrane RBFE calculation

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hannahbaumann changed the title ~~Add tutorial for membrane RBFE calculation~~ [ WIP ] Add tutorial for membrane RBFE calculation Feb 6, 2026

change to protocol_repeat 1

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hannahbaumann requested a review from jthorton February 6, 2026 14:51

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hannahbaumann and others added 2 commits February 9, 2026 09:50

Merge branch 'main' into membrane_tutorial

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Address review comments

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IAlibay mentioned this pull request Feb 9, 2026

Warning regarding validate_default OpenFreeEnergy/gufe#727

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address review comments

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hannahbaumann requested a review from jthorton February 25, 2026 08:59

hannahbaumann changed the title ~~[ WIP ] Add tutorial for membrane RBFE calculation~~ Tutorial for membrane RBFE calculation Feb 25, 2026

jameseastwood assigned jthorton Feb 25, 2026

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jthorton approved these changes Mar 2, 2026

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hannahbaumann and others added 3 commits March 6, 2026 11:08

Remove testing cells

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Add link to CLI tutorial

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Merge branch 'main' into membrane_tutorial

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IAlibay mentioned this pull request Mar 6, 2026

Add workflow_dispatch to CI configuration #296

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Merge branch 'main' into membrane_tutorial

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