ChimeraX graphical user interfaces for Phenix tools

Tom Goddard
January 30, 2025
Phenix R24 advisory meeting

R24 Aim 2:
Improve program usability and integration with other community software resources

...including an interface to UCSF's ChimeraX, a visualization and analysis program widely used by the cryo-EM community...

UCSF Team Members: Tom Ferrin, Tom Goddard, Elaine Meng and Eric Pettersen

ChimeraX

• Used by biology researchers worldwide, including almost all cryoEM labs. ChimeraX web site.
• Free for academics, paid commercial license for pharmaceutical companies.
• For interactive visualization, analysis and building of macromolecular complexes (proteins, nucleic acids, ligands).

ChimeraX Use Statistics

• ChimeraX is replacing our previous Chimera visualization software, about half of users have updated.
• 2571 journal citations in 2024, graph.
• 6500 new voluntary registrations in 2024.
• 15379 new registrations in last 3 years, database (password required).
• 5537 unique IP addresses downloaded the ISOLDE model refinement ChimeraX extension in 2024.
• 950 unique IP addresses downloaded the PhenixUI ChimeraX extension in 2024.

Journal citations per year

Registrations, voluntary, cumulative

Downloads per year

Obtaining ChimeraX User Interfaces for Phenix Tools

ChimeraX extensions are distributed through the ChimeraX Toolshed web site. Users are notified if updates are available when ChimeraX starts. PhenixUI Toolshed web page shown at left. Both ChimeraX and Phenix must be installed on the researcher's computer. Tutorial video How to use Phenix with ChimeraX by Dorothee Liebschner (2 min 28 seconds).

Current ChimeraX Phenix User Interfaces

Place waters

Local EM fitting

Fit loops

• Water placement in cryoEM density maps.
• Local EM fitting of atomic models in cryoEM maps.
• Fit loops - adds loops of up to 15 residues to an existing atomic model following density.
• Fit ligand - place known ligand in chosen map density (development in progress).

ChimeraX User Interface Development Process

• ChimeraX Phenix user interfaces are developed at UCSF by Eric Pettersen. Extensive documentation is written Elaine Meng. Tom Goddard advises on cryoEM issues.
• Phenix developers Randy Read, Tom Terwilliger, Pavel Afonine, Oleg Sobolev, Billy Poon make Phenix improvements to address any issues uncovered.
• Dorothee Liebshner creates tutorial videos.
• Monthly meetings including the Phenix and ChimeraX teams.
  • Demonstrate current tool interfaces.
  • Take suggestions for user interface improvements.
  • Discuss modifications to Phenix command to support better user interfaces.
  • Discuss Phenix command issues discovered in testing.
  • Choose next Phenix tool to interface with ChimeraX.

User Interfaces

• Atomic models and cryoEM or X-ray maps are opened in ChimeraX.
• Phenix tools are chosen from the Tools/Phenix menu.
• Panels contain many parameters and interactive controls for setting up input.
• ChimeraX button runs the Phenix command as a separate process and reads results (typically a few minutes).
• New panels display results and assist evaluating newly modeled structure.
• Details of user interfaces in following slides.

Water Placement User Interface

Input model, map and parameters

Output table of waters including number of hydrogen bonds Visualization of water selected in table

• The hydrogen bond dashed lines shown are computed by ChimeraX.
• The count is shown in the output table.
• This leverages ChimeraX hydrogen bond detection to assess water placement results.

Documentation

All user interfaces have detailed documentation shown in a web browser by pressing the Help button on the user interface. All options and mechanisms for exploring the results are detailed with cross linking to related ChimeraX capabilities.

Water placement documentation

Local EM Fitting User Interface

Video tutorial example made by Dorothee Liebschner (starting at 4:29, about 1 minute).

Input model, maps and parameters

Orange sphere placed with mouse to define fitting region.

Possible fits shown in a table Atomic model selected in table placed at fit position

Fit Loops User Interface

Input model, map and parameters

Output table of one or more built loops Visualization of new loop (green)

Fit Ligand User Interface

Input model, map and parameters

Orange sphere placed with mouse defines fitting region

Visualization of ligand fit in density

Additional Proposed User Interfaces

The current Phenix R24 proposes two additional user interfaces. We will probably develop one of them before the current grant ends.

1. Restraint specification. Allows a user to specify atomic model building constraints in ChimeraX that are then used by Phenix model building algorithms. For example:
   • the density and model in this region are great - restrain them to their starting geometry
   • I have a good reference model from elsewhere for this bit - restrain against that
   • The density here is awful, and I've basically just rigid-body docked a domain - restrain all atoms in that part to their starting positions
2. Validation. Provides a user interface in ChimeraX for researchers to examine and fix atomic model problems identified by Phenix validation tools such as Molprobity.