Add PyRosetta Interface Metrics by JoshuaMHardy · Pull Request #15 · MSDLLCpapers/ovo

JoshuaMHardy · 2026-01-22T02:28:29Z

Adds hydrogen bond counts to PyRosetta interface calculations

Issue: #10 Integrate additional PyRosetta interface scoring metrics

This pull request adds three metrics to the Ovo pipeline for RFdiffusion:

Interface Shape Complementarity (interface_sc). This was being calculated but was not in the descriptors.
Interace H-bonds (hbonds_int) - Hydrogen bonds at interface calculated by InterfaceAnalyzerMetrics mover (as done in BindCraft pipeline). This mover also calculates other metrics (listed in /ovo/pipelines/pyrosetta-interface-metrics/bin/interface_metrics_rfdesign.xml), many of which are redundant with current metrics but can be externalised if desired.
Buried Unsat H-bonds (buns_heavy_ball_1.1D) - Unsaturated hydrogen bonds at the interface. This can be calculated with or without an external program 'DAlphaBall'. Although it improves accuracy of the calculation, integrating DAlphaBall adds complexity. I've describe my implementation below.

The use of DAlphaBall in the calculation is controlled by 'dalphaball_sasa' in the Rosetta XML script. By default, this is false and the metric will be calculated without it. If a compiled DAlphaBall binary is provided, this will be switched to true by rewriting the XML file.
DAlphaBall is not portable requiring compilation with host libraries. My attempts at a statically linked binary failed. I have made a bash script (scripts/build_dalphaball.sh) called by a new command 'ovo init dalphaball' that users can use to compile it to $OVO_HOME/bin, where it will be found by the pyrosetta python script. For containers it would be best to compile DAlphaBall inside the container, as I found binding the path resulted in incompatibilities with container libraries. My documentation updates assume container integration. I'm not sure how the containers are updated but I would suggest something like the following:

# Dependencies (including gfortran/libgmp for DAlphaBall)
RUN apt-get update \
    && apt-get install -y bzip2 gfortran libgmp-dev \
    && apt-get clean && rm -rf /var/cache/apt/lists /var/lib/apt/lists

# Install DAlphaBall (for improved BuriedUnsatHbonds SASA calculations)
RUN cd /tmp \
    && git clone --depth 1 https://github.com/outpace-bio/DAlphaBall.git \
    && cd DAlphaBall/src \
    && FC=gfortran CC=gcc make \
    && mkdir -p /opt/dalphaball \
    && cp DAlphaBall.gcc /opt/dalphaball/ \
    && cd / && rm -rf /tmp/DAlphaBall
ENV DALPHABALL_PATH=/opt/dalphaball/DAlphaBall.gcc

I am interested to hear your thoughts on the implementation. Another PyRosetta metric listed in a TODO comment requires PSIPRED and I think figuring out how to integrate PyRosetta dependencies will be useful moving forwards (although hopefully they are easier than DAlphaBall).

Checklist

[ X ] Formatting is applied (just format)
[ X ] Linked to an issue above

🧩 Screenshots / Logs (if applicable)

Attach images, logs, or console outputs that help reviewers.

Copilot

Pull request overview

This pull request adds three new PyRosetta interface metrics to the OVO pipeline for RFdiffusion binder designs: Interface Shape Complementarity, Interface H-bonds count, and Buried Unsatisfied H-bonds. The PR also integrates optional DAlphaBall support for improved SASA calculations.

Changes:

Added automated detection and configuration of DAlphaBall for rotation-invariant SASA calculations in buried unsatisfied H-bond metrics
Added three new descriptors (interface_sc, hbonds_int, buns_heavy_ball_1.1D) with appropriate metadata
Implemented a CLI command (ovo init dalphaball) for conda users to build DAlphaBall locally

Reviewed changes

Copilot reviewed 4 out of 6 changed files in this pull request and generated 2 comments.

Show a summary per file

File	Description
scripts/build_dalphaball.sh	Bash script to clone, compile, and install DAlphaBall for local conda users
ovo/pipelines/pyrosetta-interface-metrics/bin/pyrosetta_interface_metrics.py	Updated to auto-detect DAlphaBall and dynamically configure XML based on availability
ovo/pipelines/pyrosetta-interface-metrics/bin/interface_metrics_rfdesign.xml	Enabled BuriedUnsatHbonds filter and added InterfaceAnalyzerMover to calculate new metrics
ovo/core/database/descriptors_rfdiffusion.py	Added three new descriptor definitions for the PyRosetta metrics
ovo/cli/init.py	Added new `dalphaball` subcommand to build DAlphaBall locally
docs/source/user_guide/installation.md	Added documentation for optional DAlphaBall installation

💡 Add Copilot custom instructions for smarter, more guided reviews. Learn how to get started.

prihoda · 2026-01-24T16:54:11Z

+    install_dir = os.path.abspath(os.path.expanduser(install_dir))
+
+    # Get path to build script
+    build_script = os.path.join(os.path.dirname(__file__), "..", "..", "scripts", "build_dalphaball.sh")


I believe this will only work when installed with pip install -e because the scripts folder is not packaged. You can either put the file into ovo/resources/ or even as an inline variable here in the init script.

on second thoughts: https://github.com/MSDLLCpapers/ovo/pull/15/files/303ddb421394f46f12405a8c2a851e93ab4791f4#r2724455334

prihoda · 2026-01-24T16:57:27Z

+    console.print("")
+
+    # Set default install directory to $OVO_HOME/bin
+    if install_dir is None:


This directory might not be mounted, but I think an elegant solution would be to store this a new bin subfolder in config.reference_files_dir (that field already contains an absolute path).

on second thoughts: https://github.com/MSDLLCpapers/ovo/pull/15/files/303ddb421394f46f12405a8c2a851e93ab4791f4#r2724455334

prihoda · 2026-01-24T17:00:56Z

+        return env_path
+
+    # 2. Check OVO_HOME/bin (where ovo init dalphaball installs it)
+    ovo_home = os.environ.get("OVO_HOME")


this is tricky because the scheduler job might not see the same env vars. Instead, you can treat this file same as we treat rfdiffusion models and add a dedicated param dalphaball_path: the pipeline's nextflow config file can use params.reference_files_dir to define a default value for it:
https://github.com/MSDLLCpapers/ovo/blob/develop/ovo/pipelines/rfdiffusion-backbone/nextflow.config#L11-L13

hmm, maybe one downside is that typically these files are required since they are declared as path... maybe if it was a val, it should handle the case when it's missing (the reference files dir will always be mounted so it should work with val as long as it's an absolute path)

in case of docker, it makes sense to keep using the DALPHABALL_PATH in the block above, so the param would not be used in that case

what if we included the dalphaball build dependencies to the conda env, and then do it as part of the main.nf script itself when not already present? Like we do for boltz mols folder: https://github.com/MSDLLCpapers/ovo/blob/develop/ovo/pipelines/boltz/main.nf#L36-L47

we already have similar logic for conda in the fastrelax script: https://github.com/MSDLLCpapers/ovo/blob/develop/ovo/pipelines/proteinmpnn-fastrelax/main.nf#L25-L34

it adds extra stuff to ./site-packages/ of that env, we could actually do the same with dalphaball.gcc, perhaps just to another subfolder... so then it wouldn't have to be a nextflow param :)

that would mean dalphaball would be required which would simplify a lot of the logic (at the cost of debugging any issues people get with installing dalphaball on the fly, but it seems like they should be rare)

I agree this is the best solution - I did not see those checks in main.nf for missing files. I have not encountered any issues with dalphaball on the fly, as long as it was compiled correctly.

prihoda · 2026-01-24T17:02:50Z

+# Adjust dalphaball_sasa based on availability
+if has_dalphaball:
+    # Change dalphaball_sasa="false" to dalphaball_sasa="true" to enable rotation-invariant SASA
+    xml_content = xml_content.replace('dalphaball_sasa="false"', 'dalphaball_sasa="true"')


might be worth adding an assert here that makes sure that the string is found, to avoid issues if someone changes the xml in the future

prihoda · 2026-01-24T17:07:36Z

-PYROSETTA_INTERFACE_DESCRIPTORS = [PYROSETTA_DDG, PYROSETTA_CMS, PYROSETTA_SAP_SCORE]
+PYROSETTA_BUNS = NumericGlobalDescriptor(
+    name="Buried Unsat H-bonds",
+    description="Buried unsatisfied hydrogen bonds at the interface (ddG-style). Uses DAlphaBall rotation-invariant SASA if available (via 'ovo init dalphaball'), otherwise standard SASA. Calculated as bound - unbound buried unsats. Lower is better.",


a cherry on top would be to use slightly different fields when dalphaball was or wasn't being used and then have two versions of the descriptor object, because without that, the description might be incorrect

one downside is that the UI would also need to handle these two versions, but perhaps the dalphaball version could be considered the primary supported one

prihoda · 2026-01-24T17:08:19Z

Thanks for the thorough implementation, I think this approach will work great! I added a few comments, please let me know your thoughts.

prihoda · 2026-01-24T17:58:59Z

+
+set -euo pipefail
+
+INSTALL_DIR="${1:-${OVO_HOME:-$HOME/ovo}/bin}"


please make this a required arg to avoid duplicate logic for setting the default path to bin dir

Minor fixes to pull request Co-authored-by: Copilot <175728472+Copilot@users.noreply.github.com>

JoshuaMHardy added 5 commits January 21, 2026 16:21

Add DAlphaBall for PyRosetta

23e1110

Fix dalphaball and add hbond count

84a169e

Add shape complementarity descriptor

eaec9ec

Container aware fix for DAlphaBall

3af9371

Switch source of DAlphaBall code

303ddb4

Copilot AI review requested due to automatic review settings January 22, 2026 02:28

Copilot started reviewing on behalf of JoshuaMHardy January 22, 2026 02:28 View session

Copilot AI reviewed Jan 22, 2026

View reviewed changes

Comment thread ovo/cli/init.py Outdated

Comment thread ovo/core/database/descriptors_rfdiffusion.py Outdated

prihoda reviewed Jan 24, 2026

View reviewed changes

JoshuaMHardy commented Feb 11, 2026

View reviewed changes

Comment thread ovo/pipelines/pyrosetta-interface-metrics/bin/pyrosetta_interface_metrics.py

Apply suggestions from code review

4e8f7bc

Minor fixes to pull request Co-authored-by: Copilot <175728472+Copilot@users.noreply.github.com>


		set -euo pipefail

		INSTALL_DIR="${1:-${OVO_HOME:-$HOME/ovo}/bin}"

Conversation

JoshuaMHardy commented Jan 22, 2026 • edited by prihoda Loading Uh oh! There was an error while loading. Please reload this page.

Uh oh!

I am interested to hear your thoughts on the implementation. Another PyRosetta metric listed in a TODO comment requires PSIPRED and I think figuring out how to integrate PyRosetta dependencies will be useful moving forwards (although hopefully they are easier than DAlphaBall).

Checklist

🧩 Screenshots / Logs (if applicable)

Uh oh!

Copilot AI left a comment

Choose a reason for hiding this comment

Pull request overview

Reviewed changes

Uh oh!

Uh oh!

Uh oh!

Choose a reason for hiding this comment

Uh oh!

Choose a reason for hiding this comment

Uh oh!

Choose a reason for hiding this comment

Uh oh!

Choose a reason for hiding this comment

Uh oh!

Choose a reason for hiding this comment

Uh oh!

prihoda Jan 24, 2026 • edited Loading Uh oh! There was an error while loading. Please reload this page.

Uh oh!

Choose a reason for hiding this comment

Uh oh!

Choose a reason for hiding this comment

Uh oh!

prihoda Jan 24, 2026 • edited Loading Uh oh! There was an error while loading. Please reload this page.

Uh oh!

Choose a reason for hiding this comment

Uh oh!

Choose a reason for hiding this comment

Uh oh!

Choose a reason for hiding this comment

Uh oh!

Choose a reason for hiding this comment

Uh oh!

prihoda commented Jan 24, 2026

Uh oh!

Choose a reason for hiding this comment

Uh oh!

Uh oh!

Reviewers

Assignees

Labels

Projects

Milestone

Development

Uh oh!

3 participants

JoshuaMHardy commented Jan 22, 2026 •

edited by prihoda

Loading

prihoda Jan 24, 2026 •

edited

Loading

prihoda Jan 24, 2026 •

edited

Loading