Prolif class implementation by talagayev · Pull Request #88 · OpenFreeEnergy/openfe_analysis

talagayev · 2026-02-18T11:36:07Z

First draft of the ProLIF implementation into OpenFE Analysis.

Changes made:

creation of ProLIFAnalysis class for calculation of interactions using ProLIF
Addition of first tests in test_prolif.py, which mainly look into if interactions were calculated sucessfully and protein/ligand conversion from MDAnalysis into ProLIF worked sucessfully.

Currently that is the first draft and PR is to see that the tests work etc.

Some notes:

Currently this is just calculating and returning the results in pd.DataFrame format, since that is easy to see if it worked. We can see what the best way is to present the results, be it 2D visualization of the interactions, dataframes or some other format.
As was mentioned by Irfan, the recognition and conversion of protein in MDAnalysis is sometimes tricky, which is the case here. So the code currently needs to guess bonds, which it does here:
universe.select_atoms("protein").guess_bonds(vdwradii=vdwradii)
But for the vdwradii it wants some values for Cl, Br etc. that we need to provide, so we need to see what defaults we select there.
For interactions we need to check what the default option should be, if default == all interactions or some interactions etc. and if the water-bridge interactions are default and if so, what water-bridge interaction order we make default. the current one is 3, which means it can be something like:
Ligand -- Water -- Water -- Water -- Protein
Same goes with ProLIFAnalysis.run() there we can also look into what the defaults have to be, how many cores and if the interactions should be atom based (Ligand with Protein atom) or residue based (Ligand with Protein residue).

This is the first draft, will be updated during further development :)

PS. A small thing I also noticed, since I tested it on different PCs with one being with Windows currently somehow python 3.14 has module loading Issues with rdkit and thus I had to downgrade there to python 3.13.

codecov · 2026-02-18T11:38:17Z

Codecov Report

❌ Patch coverage is 72.22222% with 30 lines in your changes missing coverage. Please review.
✅ Project coverage is 93.15%. Comparing base (c1bdddc) to head (15e8620).

Files with missing lines	Patch %	Lines
src/openfe_analysis/prolif.py	72.22%	30 Missing ⚠️

Additional details and impacted files

@@            Coverage Diff             @@
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  Lines         462      570     +108     
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+ Hits          453      531      +78     
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IAlibay · 2026-02-18T11:41:30Z

+import prolif as plf
+
+
+class ProLIFAnalysis:


Can you subclass AnalysisBase here?

Yup should be doable, will look into it :)

Wanted to wait and see how RMSD will look like to use an identical structure and have this initial PR to have bulletpoints to discuss tomorrow during the meeting and also have an easier overview on what was changed etc. :)

jthorton · 2026-02-19T11:39:47Z

I am not sure if this should be handled in the analysis class or in a protocol before running this class but there is an issue when doing this kind of analysis on trajectories from our hybrid topology protocol, where the connectivity of the end state ligands and identities of the atoms can get confused see this example on end stateB when looking at torsions. Should we add an option to provide and rdkit molecule for the ligand and use this to correct the ligand atom group automatically or should we have users fix this beforehand? This will be needed in the torsion analysis as well so a general function which could fix an atom group might be a good idea?

hannahbaumann · 2026-02-26T12:57:20Z

+
+        # Currently adding here but maybe as args?
+        self.protein_ag = self.universe.select_atoms(
+            "protein and byres around 12 group ligand",


Yes, I agree I think it would be great to have these (also for water below) as args.

hannahbaumann · 2026-02-26T12:59:14Z

+            and "WaterBridge" in fp_interactions
+        ):
+            if self.water_ag.n_atoms == 0:
+                raise ValueError("WaterBridge selected but water selection is empty.")


Maybe instead raise a warning, or what would happen if there are individual frames that don't have water molecules?

Yes warining would be better in that case, since that is quite a possible scenario, best approach would be truly warning + remove the water_bridge interaction so that it doesn't run when there are no waters, since I would need to check, but I think currently it would possibly still try to run it 🤔

jthorton · 2026-03-26T16:21:18Z

+                vdwradii = {
+                    "Cl": 1.75,
+                    "CL": 1.75,
+                    "Br": 1.85,
+                    "BR": 1.85,
+                    "Na": 2.27,
+                    "NA": 2.27,
+                }


Can we use the vdwraddi from here https://github.com/MDAnalysis/mdanalysis/blob/develop/package/MDAnalysis/guesser/tables.py#L310

…FreeEnergy/openfe_analysis into prolif_class_implementation

hannahbaumann

Thanks @talagayev , this looks good! The main part I'm not sure about is the run function, maybe we can discuss that tomorrow!

hannahbaumann · 2026-04-22T10:42:53Z

+            self.ligand_ag.guess_bonds(vdwradii=vdwradii)
+
+            # Water: only if you care about water-mediated interactions
+            if guess_bonds:


This should always be true since the outer loop goes through the same. Or did you mean to put something else here?

hannahbaumann · 2026-04-22T11:13:34Z

+            # Cover case of false interaction
+            missing = [i for i in interactions if i not in available]
+            if missing:
+                raise ValueError(


It looks like ProLIF would also raise an error for missing interactions, so this may not be necessary.
_check_valid_interactions

hannahbaumann · 2026-04-22T11:16:42Z

+        if fp_interactions is None:
+            self.fp = plf.Fingerprint(parameters=self._parameters)
+        elif len(fp_interactions) == 0:
+            self.fp = plf.Fingerprint(parameters=self._parameters)


Here we could also use a if fp_interactions: to handle both cases, None and empty list.

hannahbaumann · 2026-05-19T10:31:41Z

+        self.ifp_df = None
+
+        # --- Guess bonds once on stable selections so RDKit/ProLIF can detect HBonds ---
+        if guess_bonds:


There's a lot happening in init here, maybe it would make sense to put some of these into private functions (e.g. to guess bonds, to build the fingerprints) so that they are easier to test separately and for a better overview of the different things that are going on.

agree, can split it up a little bit, since it is quite crowded currently

@talagayev i created a small utils function for the guessing of bonds here :

openfe_analysis/src/openfe_analysis/utils/universe_utils.py

Line 60 in aae4531

def guess_ligand_bonds(

as part of this PR #92
Please let me know what you think about it!

@hannahbaumann looks good to me, will adjust the code to import it from there :)

hannahbaumann · 2026-05-28T08:51:49Z

  - openff-units
  - pip
  - tqdm
+  - prolif


Could you also add the dependency to the pyproject.toml?

Yes can do :)

hannahbaumann · 2026-05-28T08:53:23Z

+        guess_bonds: bool = True,
+        vdwradii: Optional[Dict[str, float]] = None,
+    ) -> None:
+        """


In the other analysis classes we ended up going with the doc string style of putting the doc string at the function level instead of having it in init. Could you maybe change that here as well?

hannahbaumann · 2026-05-28T09:00:39Z

+            show_interaction_data=show_interaction_data,
+        )
+
+    plot_2d = plot_lignetwork


Maybe we could also rename the function above to plot_2d or similar and remove the alias here?

hannahbaumann · 2026-05-28T09:01:42Z

+        """
+        2D ProLIF ligand-network visualization.
+        """
+        if not self.ifp:


This could also be a small helper function since the check is done for all three plots.

True true :)

hannahbaumann

Thanks @talagayev , this looks good! Just left a few more comments, please let me know if you have any questions!

hannahbaumann · 2026-05-28T09:03:35Z

+        Transform fingerprint results to pd.DataFrame.
+        """
+        df = self.fp.to_dataframe(**kwargs)
+        self.ifp_df = df


I'm not sure if it's necessary to store it here.

hm seing the dataframe and with the dataframe being also kinda a quite utils style representation of results I am thinking if it makes sense if we would have other cases where we would want to show results in dataframes just as an utils function accesible for all other functions 🤔

talagayev · 2026-05-28T09:18:30Z

Thanks @talagayev , this looks good! Just left a few more comments, please let me know if you have any questions!

Yes probably a short one. Didn't have time to push the commits that I worked on yesterday, but for the plotting I wanted to ask about the plot_3d and plot_lignetwork. With the plot_barcode being quite generic I rewrote it a little bit to be possible to be used with other inputs and moved it to plotting.py, but the plot_lignetwork is quite ProLIF unique so should we leave it in prolif.py and for plot_3d currently it does uses again a function directly from ProLIF, but overall if we will use py3Dmol to visualize in 3D in other functions I can also rewrite it to be more generic to be accesible for other functions 🤔

talagayev added 2 commits February 17, 2026 22:51

added prolif in environment.yml

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black format

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IAlibay reviewed Feb 18, 2026

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talagayev added 3 commits February 26, 2026 00:31

modified for AnalysisBase

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added tests

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hannahbaumann reviewed Feb 26, 2026

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Merge branch 'main' into prolif_class_implementation

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jthorton reviewed Mar 26, 2026

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talagayev and others added 8 commits April 16, 2026 00:41

Added 2D visualizationa and adressed comments

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Added tests

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added args for selection

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Merge branch 'main' into prolif_class_implementation

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adjusted test error

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Merge branch 'prolif_class_implementation' of https://github.com/Open…

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…FreeEnergy/openfe_analysis into prolif_class_implementation

adjusted tests

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talagayev requested review from hannahbaumann and jthorton April 22, 2026 09:52

hannahbaumann reviewed Apr 22, 2026

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adjusted code to add additional visualization and changed the wrapper

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hannahbaumann reviewed May 19, 2026

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hannahbaumann self-assigned this May 21, 2026

This was linked to issues May 21, 2026

prolif hook #22

Open

Protein-ligand contact analysis #6

Closed

talagayev and others added 2 commits May 27, 2026 23:59

Merge branch 'main' into prolif_class_implementation

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Merge branch 'main' into prolif_class_implementation

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hannahbaumann reviewed May 28, 2026

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hannahbaumann requested changes May 28, 2026

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talagayev commented May 28, 2026

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