Work in progress March 13 - May 22, 2025

Tom Goddard
May 22, 2025
Group meeting

Topics

• Boltz structure prediction tool
• Future plans for improving structure prediction

Boltz structure prediction

• Boltz is a structure prediction program derived from AlphaFold 3 with similar accuracy to AF3.
• Predicts assemblies of proteins, DNA, RNA, ligands, ions, solvent.
• Created by PhD candidate Jeremy Wohlwend in the Regina Barzilay lab at MIT.
• Fully open source, MIT license. AlphaFold 3, Chai-1 and other ML structure prediction programs do not provide training code preventing the research community from improving the prediction method.
• bioRxiv preprint

Documentation

• ChimeraX Boltz tool web page, and User Guide documentation.
• ChimeraX Boltz demonstration video.
• BlueSky announcement.

ChimeraX Boltz structure prediction tool

ChimeraX Boltz structure prediction tool will be in ChimeraX June release.

Boltz tool GUI

• New capabilities it adds:
  1. Predict structures with ligands and ions and nucleic acids.
  2. GUI to flexibly specify proteins, nucleic acids, ligands in various ways.
  3. Much faster than Colabfold / AlphaFold 2.
  4. Runs on local computer, one button install of Boltz on local machine (Mac, Windows, Linux).
  5. Easier specification of molecules to predict by using structures opened in ChimeraX.

• Implementation challenges:
  1. Estimate time for each job to plan predictions of large complexes that could take hours.
  2. Allow queueing many jobs to run sequentially and in background.
  3. Boltz uses Colabfold MSA server which is heavily loaded. May want UCSF MSA server.
  4. Boltz needs to read SDF format ligands to easily handle covalent linking, currently only CCD or SMILES.

Future Boltz improvements

• ChimeraX Boltz improvements ticket
• bfloat16 boltz pull request.
• waters boltz pull request.