Hi Gerardo,

  I made an example ChimeraX command "modelcif pae" that reads pairwise scores included directly in the ModelCIF structure file and shows them as an AlphaFold PAE plot.  Here's the code and an example using it

https://rbvi.github.io/chimerax-recipes/modelcif_pae/modelcif_pae.html

To handle all the cases you describe well would take more work, for example, where the scores are in separate files and need to be fetched.  And the user should be provided a list of scores if more than one is available.  And scores where you might want to show high values (e.g. probability) instead of low values won't work well with the ChimeraX "alphafold contacts" command which shows interactions between domains but is designed for predicted aligned error (PAE) values and filters to only show low values.  And how to handle sparse values (where every residue pair does not have a score) needs some more thought.  For that I made a defaultScore option so the full matrix of all-by-all residues is first filled with the default score.

  Properly handling all the cases of more general scores than AlphaFold PAE is a good bit of work and would likely be used far less than AlphaFold PAE, so I'm not sure I can justify the effort to support all those capabilities.  But maybe this start I made will encourage someone else to provide a more complete extension to ChimeraX.

Tom

pombe_h3_h4_dpb3.pngpombe_h3_h4_dpb3_pae.png

On Sep 26, 2024, at 11:42 AM, Gerardo Tauriello via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:

Dear ChimeraX developers,

Following up on discussions in https://github.com/chaidiscovery/chai-lab/issues/52 and the large amounts of models which have been deposited in ModelArchive (MA; https://modelarchive.org/) in the meantime, I would propose to support loading PAE (or other local-pairwise scores) values from ModelCIF files as used by MA.

Here I link some examples which should capture most use cases:
  1. ma-bak-cepc-0944 includes 2 local-pairwise scores (PAE and "contact probability") and only stores scores for inter-chain residue-pairs.
  2. ma-dm-hisrep-003 includes a full PAE matrix.
  3. In all cases in MA, entries contain a single accompanying zip file which also contains the local pairwise scores which are extracted into a separate file to keep the main ModelCIF file at a manageable size. The linked modelcif_examples_for_chimerax.zip package includes pae_associated_file where the pairwise scores are directly in a separate file instead of being in a zip file and pae_in_main_file which includes the pairwise scores directly in the main ModelCIF file.

Already now ChimeraX is able to parse the ma_qa_metric_local category in ModelCIF to do per-residue coloring for pLDDT etc which is awesome.
To make sense of ma_qa_metric_local_pairwise one needs the following (I try to be detailed to simplify the implementation):
  1. Parse ma_qa_metric and keep the IDs (_ma_qa_metric.id) for rows with ma_qa_metric.mode == "local-pairwise". If we want to restrict this to PAE matrices, one would additionally check that_ma_qa_metric.type == "PAE".
  2. Look for the _ma_qa_metric_local_pairwise category. There are 3 options on where to find it:
    1. Directly in the main ModelCIF file (as in pae_in_main_file/003-Spombe_H3-H4_tetramer_DPB3.cif).
    2. In a separate file via _ma_entry_associated_files (as in pae_associated_file/003-Spombe_H3-H4_tetramer_DPB3.cif). You can find the file via _ma_entry_associated_files.file_url for the _ma_entry_associated_files row with file_content == "local pairwise QA scores".
    3. In a separate file via _ma_associated_archive_file_details (as in all MA entries such as ma-bak-cepc-0944 and ma-dm-hisrep-003). Procedure to get it:
      1. Find row in _ma_associated_archive_file_details with file_content == "local pairwise QA scores" and keep archive_file_id and file_path.
      2. Find zip file in _ma_entry_associated_files with id == archive_file_id and download via file_url.
      3. Fetch file named file_path from that zip file.
  3. Within the _ma_qa_metric_local_pairwise extract scores for all given residue pairs for metric_id matching the desired IDs from step 1. Each residue is identified with model_id, label_asym_id, label_seq_id, and (redundantly) label_comp_id. There are no guarantees on the order of the data or completeness of the data but each referenced residue is guaranteed to exist in the atom_site category.

Here is the current list of model sets in MA which include PAE matrices: ma-bak-cepc, ma-coffe-slac, ma-tbvar3d, ma-ornl-sphdiv, ma-t3vr3, ma-low-csi, ma-ombbaf2, ma-rap-bacsu, ma-nmpfamsdb, ma-jd-viral, ma-dm-prc, ma-dm-hisrep, ma-osf-ppp2r2a.
All together MA has over 200'000 models with PAE matrices which all supplement the AFDB in some way (e.g. protein complexes, viral proteins and other proteins not covered in UniProt).

It would be great to include support for ModelArchive's ModelCIF files in ChimeraX and I am happy to provide further information and help as needed.

Regards,
Gerardo

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