ChimeraX: Next Generation Molecular Graphics

Advisory Committee
March 25, 2015

What is ChimeraX?

• ChimeraX is our next generation molecular visualization software following Midas, MidasPlus and Chimera.
  • Modernize user interface
  • Emphasize performance
  • Familiar user interface but not backwards compatible with Chimera
  • Improve support for community plugin developers

• Original Chimera (henceforth "Chimera 1") initially released in year 2000. Since then:
  • Increase in computer performance, CPU 50x, graphics 100x, disk space 200x, network 50x.
  • Increase in data size and coverage: molecular structures, sequences, and density maps.

• Development effort during the past year
  • 75% on ChimeraX
  • 25% maintaining Chimera 1

New Technologies and Capabilities in ChimeraX

• Advanced graphics using GPU programming.
• High performance handling large models or hundreds of models.
• Unique capabilities.
• New user interface toolkit, rich html log output.
• Web browser apps using WebGL.
• Community plugin development, distribution system, stable programming interfaces and docs.

Advanced graphics using GPU programming

• Modern 3D graphics uses low level GPU programming that enables new rendering effects and maximum performance.
• Chimera 1 was based on older OpenGL using a limited library of functions.
• Many benefits:
  • Ambient occlusion lighting for better depth perception
  • Selection outlines 5x faster than Chimera 1
  • Silhouette edges up to 100x faster than Chimera 1
  • Several times faster rendering of large cellPACK models containing thousands of molecules.

Ambient occlusion lighting. GPU programming allows interactive speed with 100 cast shadows.

	Virus capsomere PDB 1m4x	Chaperonin PDB 1aon	70S ribosome PDB 4v63	Bacteriophage T7 EMD 6035
Chimera 1
ChimeraX ambient shadows

Fast selection outlines.

Fast silhouette edges.

Fast molecule copies. 20,000 molecule HIV model.

High performance handling large models or hundreds of models

• Open and display molecules 10x faster than Chimera 1, e.g. HIV capsid model, 2.4 million atom, in 10 seconds.
• PDB provides single mmCIF file for entries over 100,000 atoms, no longer has multiple ids. December 2014.
• We worked with John Westbrook, mmCIF architect at RCSB, to optimize format.
• Fast display of hundreds of medium size models helps comparative modeling.

HIV capsid, 2.4 million atoms, 3j3q.cif	106 PDB models matching fibronectin sequence P02751

Reliable algorithms for large models: surface and area calculations

• Chimera 1 molecular surface and area calculations fail on many structure over 10000 atoms.
• Hundreds of users have reported this problem.
• ChimeraX has new solvent excluded surface calculation works for all structures, 30x faster.
• Surface and area calculation can use multiple cores.
• Demonstration: computing areas between all molecules in large complexes, RNA polymerase 1k83.

Unique Capabilities

Some examples:

• Graphs and networks using Cytoscape and NetworkX.
• Visualization of density map time series
• Oculus Rift immersive visualization

Density Map Time Series

• Migrating neutrophil (hl60) cells demonstration in ChimeraX.
• Preprocessing makes multiresolution HDF5 file, removes jitter, compensates for photobleaching.
• Mask to show only collagen near cell.
• Quantify motion, centroid velocity, cell size, inertia axes, collagen deflections.

Movie of cell motion.	Collagen only near cell path.	3-D printed cell.

Cell centroids (orange dots), size and axes (blue ellipsoid).		Plot cell speed and size changes.	Visualize filament motion (green and red prickles).

Immersive Visualization

Oculus Rift goggles give 360 degree view. More for inspiration than analysis. View inside the a network of collagen filaments. Demo at lunch. Collaborator Dyche Mullins: "Now I know what it feels like to be the cell!"

New user interface toolkit: Qt Widgets

• Dockable panels. Demonstrate.
• HTML for work log with images, sessions, links, movies.
• Chimera 1 toolkit Tk has only life support maintenance.
  • Example problem: Dual display Tk crash reported 60 times by Chimera 1 users.
  • Took 80 hours to diagnose and patch our code to avoid Tk bug.

...

Web browser apps based on WebGL

• Offer web browser applications derived from ChimeraX code.
• All major web browsers support WebGL 3-D graphics.
  • Safari, Internet Explorer, and iPad/iPhone support added summer 2014.
  • Allows same graphics performance in web browser as desktop apps.

Example: Map series web application

• 5 people in 3 labs at UCSF analyze Dyche Mullin's cell migration data.
• Data is on a server.
• Share placed marker and note annotations. Collaborative data analysis.
• No software installation.

Example: Protein sculpture design web app

• Box beam protein backbone sculptures made by sculptor Julian Vos-Andreae.
• Developed Chimera 1 extension to produce beam cutting instructions.
• Converted to web app to allow others to make sculptures.
• Collaboration with Daniel Gurnon at DePauw University and sculptor Julian Voss-Andreae.

Alpha helix at Linus Pauling house.	Hemoglobin	Sculpture design Web app.

Community plugin development

• Offer ChimeraX plugin distribution, version checking, and stable programming interfaces.
• Many Chimera 1 plugins created by outside developers, about 50 developed by 20 labs.
• Chimera 1 plugin difficulties:
  • Hard for users to find useful plugins. Every developer distributes on their own web site.
  • Plugins break after a few Chimera releases.

Tool shed distribution system

• ChimeraX user interface shows all available plugins from a central repository.
• Install with one click.
• Plugins that require other plugins automatically handled.
• Version compatibility checked.
• Stable and documented ChimeraX programming interfaces (APIs).
• Also get latest Chimera bug fixes with one click.
• Backend is working with primitive test user interface (image).

ChimeraX Status

• Currently unreleased
• Target 0.x release in early 2017
  • Will include demonstrated new features
  • Will have a small subset of Chimera 1 functionality
  • Handle molecule, sequence and density map data.
• Currently working on sequence code.
• Stable programming interfaces for developers in a later release.