NIAID contract progress November 17, 2022 - Feb 1, 2023

Tom Goddard
February 2, 2023
Group meeting

NIAID contract progress

• Eric - NIH 3D pipeline
• Greg - Improved mmCIF reading
• Zach - DICOM
• Elaine - documentation for contract features
• Tom - machine learning structure prediction for cryoEM and VR

Draft NIAID 2023-24 contract

• Refine draft statement of work Google doc.

Machine learning

Protein structure prediction: AlphaFold and ESMFold

• ChimeraX AlphaFold use: 47021 predictions by 8892 unique IP addresses through September 2022
• AlphaFold 2.3 for predicting larger complexes with Sergey Ovchinnikov at Harvard
  • Sergey updating ColabFold to use Alphafold 2.3.1.
  • Sergey merged my ColabFold pull request to simplify ChimeraX use.
  • Updated wynton databases and singularity image to AlphaFold 2.3, postdoc Rakesh Ramachandran in Sali lab
  • Tested 1500 and 2500 and 5000 amino acid predictions on Google Colab, minsky, Wynton
  • Studied FastFold, an AlphaFold alternative, from HPC-AI-Tech, Singapore company
• Machine learning ensembles Tom Terwilliger at Sandia National Laboratories
  • Read and discussed his AlphaFold accuracy biorxiv preprint
  • Provided Tom info to directly use our fast kmer AlphaFold database search
  • Tried alphafold on 2 fold-switching proteins, all similar seqs gave same fold
• Maintenance
  • Made web page explaining how to run alphafold on Wynton.
  • Made ESMFold and AlphaFold support all the same commands and GUIs.
  • Fix ChimeraX AlphaFold broken by jax library updates, Google Colab python 3.8 update, ansi vs utf-8 encoding Colab issue.
  • Answer AlphaFold questions every week on YouTube.

IsoNet fills in missing wedge in electron tomography of cells

Neural synapse vesicles in xy plane sharp, but blurry in xz and yz planes.	IsoNet filtering sharpens xz and yz planes.

• IsoNet discussed at CZI workshop, also with Tom Laughlin, Sam Li, and John Sedat at UCSF.
• VR of neuron with IsoNet with tilted slab rendering is nice
• Installed and ran IsoNet chromosome tomograms from John Sedat

ChatGPT

• Tried making ChatGPT artificial general intelligence web chat-bot write ChimeraX Python scripts, lies admirably.
• ChatGPT is developed by OpenAI at 18th and Folsom St in San Francisco.
• ChatGPT is better at writing cheesy poems than code.

    ChatGPT: Please write a poem about Chimera molecular visualization software

	Chimera, the visualization tool so grand,
	Molecular worlds, at our fingertips in hand.
	It brings to life, what once was just a dream,
	With stunning graphics, making science supreme.

	From proteins to DNA, it shows us the way,
	The secrets of life, in a clear, concise way.
	With colors and shapes, it reveals what's unseen,
	The beauty and complexity of the molecular scene.

	It's more than a tool, it's an art and a science,
	A creation of brilliance, with a high reliance.
	It allows us to delve, into the mysteries of life,
	And understand, what once was filled with strife.

	So here's to Chimera, the tool of the hour,
	The visualizer that gives science its power.
	It's a source of wonder, for all those who know,
	The value it brings, continues to grow.

	So use it with care, and let it shine,
	For Chimera, is truly a gift divine.

Virtual reality

Enduvo GLTF color support

• Investigated Enduvo VR GLTF support for colors in molecular models for Phil Cruz.
• After months of back and forth emails with Enduvo got latest version 2.6.0.
• Enduvo support Chris Princiotta and engineer Justin Drawz helped.
• Conclusion: Enduvo only supports single color models.

Using standalone VR headsets like Quest 2 for molecules and images

• Tested existing VR apps: Gravity Sketch VR, VR Model Viewer both abandoned, Arkio architecture tour app.
• Studied pros and cons of making standalone Quest 2 app for Chimerax models.
• Studied glTFast Unity GLTF reader for making a standalone viewer app.
• Wrote Unity app to show sars-cov-2 spike obj model with OpenXR API.
• Mike Schmid at Stanford wants to do Quest 2 VR demo of tomograms at West Coast Structural Biology Workshop, March 19-22, Asilomar.

VR of cell electron tomography

• Cell electron tomography volumetric rendering in VR with IsoNet ML image filtering.
• Tried looking at John Sedat chromosome images from recent 4 papers.
• Studied how to get more sensitive brighness adjustment at high opacity with >30 volume planes.

Other ChimeraX progress

New Collaborations

• Jonathan Ramirez and Wendell Lim want to 3D print hundreds of interacting molecular models for use during research discussions.
• Arthur Charles-Orszag in Dyche Mullin's lab studying archaeal cell dna/segA/envelope. Helped show cell surfaces in structured illumination 3D microscopy.
• Ben Webb in Andrej Sali lab, proposing HDF5 format mmCIF extension for ensemble coordinates for integrative hybrid models.

ChimeraX Tutorial Presentations

• Gave insulin receptor ChimeraX in-person tutorial for UCSF Macromethods course, 90 minutes, Klim Verba and John Gross
• Gave opioids ChimeraX in-person tutorial for Inquiry Immersion drug discover course, 90 minutes, Jaime Fraser and Aashish Manglik

Segmentation File Format from EM Databank Paul Korir zoom meeting to discuss EMDB segmentation archiving Discussed EMDB subtomogram particle file formats with Utz Ermel (ArtiaX developer) and Paul Korir Fixed ChimeraX EMDB SFF reader to use new APIs, Martin Schorb (EMBL), Paul Korir (EBI) Working on segmentation alignment transforms for EMDB SFF, Paul Korir, Martin Schorb

Segmentation of cell nuclei from Martin Schorb at EMBL using new EMDB segmentation file format.