NIAID Guidehouse/MSC contract May 1, 2022 - Feb 28, 2023

1. General ChimeraX improvements to support NIAID.
   1. Specific improvements to assist NIAID personnel to transition away from the unsupported legacy Chimera program, e.g.:
      1. Join disconnected peptide segments via a new peptide bond
      2. Renumber residues
      3. Rename chain identifiers
      4. Provide both PDB and UniProt residue numberings
      5. Prepare structures for input to docking programs (remove alternate atom locations, add missing side chains, etc.)
      6. Energy minimize atomic structures
      7. More GUIs (specifically copy/combine)

2. Support the NIH 3D pipeline development, including any changes to ChimeraX to support ongoing development.
   1. Revamp NIH 3D scripts to use new presets
   2. As the pipeline code matures and reaches deployment, support for any changes to NIH 3D scripts, or ChimeraX itself, needed for optimal pipeline utility.
      1. Improved GLTF output to automatically center models at origin.
      2. Tested new PDB assembly single model mmCIF files.
   3. Perform early testing on the NIH 3D web site and provide feedback.

3. Virtual reality for molecular structure, cryoEM and medical imaging.
   1. Setup mixed reality video capture at BioVizLab on NIH campus.
   2. Allow meeting participants to add models from local files during a VR session.
      1. For this round, this may be a minimal viable project – perhaps for small files only.
   3. Add a VR toolbar in the ChimeraX interface.
   4. Add a method to save sessions in VR.
   5. Improve visualization of 3D medical imaging data in VR.
      1. Improved interface for manipulating the visualization – e.g. Medical Imaging Toolbar
   6. Support making or editing interactive 3d image segmentations in VR.
   7. Provide local interactive molecular dynamics in VR.
   8. Create video tutorials for how to use multi-person VR.
   9. Hold VR meeting office hours to train researchers to use VR capabilities.
   10. Other VR improvements.

4. CryoEM modeling utilizing machine learning structure prediction.
   1. Provide a structure prediction service (e.g. AlphaFold or RoseTTAFold) that can handle more than the 1000 amino acids possible on Google Colab.
   2. Provide visualization of machine learning structure quality metrics in 2D plots and on the structure itself to evaluate correctness of domain packing.
   3. Provide ability to specify structure templates when making predictions.
   4. Provide more reliable multiple sequence alignments (e.g. with mmseqs2) to allow structure predictions where current sequence alignment (e.g. with hhblits) fails.
   5. Provide reliable energy minimization of predicted structures.
   6. Other cryoEM machine learning structure prediction.

5. DICOM
   1. Improve DICOM reader by including more data types such as segmentations, lossless JPEG used in clinical scans, and 16 bit image data.
   2. Investigate implementation of a DICOM metadata browser

6. Outreach
   1. Instructional material and tools documentation.
      1. Detailed instructions for all features shall be provided in a user manual.
      2. Written user guides and tutorials shall be available as an HTML page.
      3. Create videos demonstrating new capabilities.
      4. Present tutorials at webinars and workshops training to use new capabilities
   2. Attendance at meetings or workshops as required by NIAID

7. Administration
   1. Submit monthly written reports of accomplishments

Meeting Minutes

2/9/2023

Phil, Meghan, Kristen; Eric, Elaine, TomG, Zach

Phil and Meghan were in a meeting with Andy (U of Indiana expert in user studies) just now. Would like to set up 3-way meeting (Andy, UCSF folks at least Tom G, NIAID folks at least Meghan) to figure out tasks for comparing VR and desktop interactions. Andy has not used ChimeraX and is thinking of everything in VR as a mesh model, not molecular data per se. We don't want to overgeneralize the study, but limit it to ChimeraX molecular data visualization. Andy may be able to get some students to work on the project this summer.

Darrell won't be able to make this meeting.

Continued SOW discussion. Need to whittle down from >3 FTEs to 2. Scooter is running through the document and describing individual items, as well as our initial suggestions of which items to drop.

2/2/2023

Phil, Meghan, Michal, Darrell; Eric, Elaine, TomG, Zach

We will meet again in one week.

(notes also exist in the 2023 NIAID SOW (DRAFT) document)

Phil is going to a meeting in Ventura and is trying to figure out how to set up a shared VR setting between two laptops. They are concerned that given that hotel wifi's might not be good enough to support VR. The plan is to set up a private network, but are concerned that they may run into problems without internet access.

Phil and Megan brought up a possible collaboration with the University of Indiana to perform actual user studies. Possible multiple tracks:

• Expert usage where the user is an expert that is experienced and knows the details of the data.
• Expert in related fields who are not as experienced in the 3D world or tools specific to the data sets.
• Possible novice users

Major milestone for this year is to get ChimeraX on the NIAID self-service software download.

1/26/2023

Schedule is not shifting - we will meet again next week because it is time to get the next SOW written.

This time we can just extend the existing contract, but with a new SOW.

DICOM - Scooter: continue work, with areas including handling more diversity of datasets/datatypes; segmentation; presets (windowing, lighting, transparency handling). Darrell: we appreciate the ChimeraX quality of rendering and being able to manipulate fairly large data without stuttering. At the same time we don't want to duplicate Slicer, or only support tools we ourselves would use... we want to benefit the larger research community. Phil: would like easier ability to set windowing/leveling in VR, especially of complex presets with multiple peaks/colors. Just making the Volume Viewer histogram a lot bigger may help. TomG: you can do it with any tool in VR by clicking both controllers' panel-showing buttons at the same time and dragging apart. Everybody: wow, didn't know that! TomG: Enhancing windowing/leveling vr mode to show visual heads-up display of histogram and curve would make it easier to use.

NIH3D - put all pipeline-associated code on github. Eric: is already on github. Scooter: maybe needs to be more evident/obvious. Darrell: may just be for NIH3D website to add a link(s) if you let ue know what they are. Also, make sure relevant bundles on Toolshed are amply documented there. Scooter: we can add the usual "continue to support NIH3D pipeline" to cover any other needs that arise.

Scooter: what can we do to support/promote use of your BioVis Lab visualization wall? Meghan: so far the networking aspect has occupied us, rather than the content of the display. Scooter: may need to handle menuing differently, for example. Maybe as you get more experience with it, please do give feedback on interface issues. Eric: and for selection, rather than Ctrl-click... Darrell: the wall is multitouch (infrared plane). Also it's not just extra-large but ultrawide. Phil: need to check out how it works with tiling. TomG: the multitouch might already work in some capacity. Meghan: Yes, some multitouch does work with ChimeraX on wall. TomG: Might use extra wide display to show multiple independent camera views.

Greg: is anybody getting one of those Acer laptop monitors with autostereo? Scooter: reviews have not been that good. We could purchase a widescreen monitor to investigate some of these issues. Meghan: speaking of hardware, could you get a Quest Pro with passthrough video? We have two. Allows all to see each other in VR, not as "Picasso heads." Quest Pro already lets you see room in peripheral vision if blinder attachments not used. TomG: depth-sensing can be tricky with these pass-through cameras, maybe room video is placed always behind computer generated objects.

Scooter: also on the list, exporting a ChimeraX session for Quest2 VR (as detailed in email from TomG 1/25/23)

Scooter: last thing on my list, exploring pedagogical benefits of VR vs. laptop/desktop screen. Anything else?

Darrell: keep level of effort about the same as last year.

Phil: maybe this falls under NIH3D umbrella, have you heard anything more from Enduvo? TomG: no. Phil: I need to contact them soon, will prod them about this. TomG: was using Enduvo 2.6.0 experimental version, with gltf warnings... lack of colors may relate to that, maybe they are not supporting gltf well. Phil: they "support" many formats but level of support may not be very high. I could get surfaces of different colors but other things like ribbons were white. TomG: each surface is a single color, though. So Enduvo can show single color per object. ChimeraX ribbons use vertex colors, not single colors, which is come up as white in Enduvo. Phil: Enduvo may not handle vertex colors regardless of format. TomG: Could enhance ChimeraX GLTF output to use single colors and separate objects.

Kristen: one open issue for NIH3D, not showing zinc atoms #8218. Eric: again an EBI assembly file for NMR structure. Greg: something about disjoint sets of atoms? TomG: works in daily build. Greg: was same problem as another ticket that has been fixed. Will close ticket.

Meghan: haptic feedback on hydrophobic/hydrophilic or ESP? Elaine: need something with a gradient, and also we don't have a full interaction energy calculation (e.g. no VDW/steric component), so it wouldn't be very helpful for manual ligand docking. Maybe fitting atoms into density? TomG: this is just a vibration, not a force, so may not be very helpful/intuitive. Scooter: maybe number of contacts/clashes could translate to strength of vibration. Eric: will have to see if the continually updating clashes would slow down VR rendering. TomG: VR haptics useful for toolbar button clicks and user interaction cues.

Darrell: maybe SOW could say "investigate utility of haptics" and maybe it could be part of a paper on pedagogical benefits of VR. Darrell: if some type of haptic feedback is associated with popular VR hardware, more people would have it. Whereas something like Phantom with a more complete haptic interaction is expensive and very few users would have access.

Scooter: we will work on the writeup and get back to you, hopefully to have time to refine in our meeting next week.

1/19/2023

Phil, Kristen, Michal, Darrell; Eric, Elaine, TomG, Greg, Zach

Darrell: next week is better, for Megan, myself, Phil, Scooter... let's reschedule to next week 1/26 instead, to discuss plans for the SOW. Kristen had some updates but not urgent, can wait until next week.

Elaine: will do

1/5/2023

Phil, Kristen, Michal, Darrell; Eric, Elaine, TomG, Scooter, Greg, Zach

Scooter: Any issues with NIH3D? Kristen: Just released beta, only 2 failures left of the 33 we had before - Phil will take a closer look. We may still want some tweaks on what is displayed or its style. Tom and Greg were looking at some weird cases. Tom: it was an mmCIF pdbe_biounit assembly file for 2miv with unusual grouping of the atoms... we suspect it is wrong formatting from them. We have a ChimeraX ticket for this with details. Probably the ChimeraX mmCIF reader should give a warning about this issue, but does not currently. Eric: in ticket #8218, 2jtn pdbe_biounit has the same problem.

Kristen: some mmCIFs didn't get their symmetry applied automatically. Eric: ticket #8170, has been fixed.

Greg: adding symmetry copies may not work for small-molecule CIF.

Phil: shows 2D ibuprofen for which several extra bonds appeared. Elaine: often these 2D diagrams are not only flat, but also have really short distances between the atoms, causing extra bonds to be added. Darrell: garbage in, garbage out. How much effort do we want to put into detecting these 2D chemical diagram cases and warning the user?

Eric: currently there is just an informational message if the approach of removing all bonds and recalculating them back would add too many bonds (in which case it reverts to the original set of bonds). Phil: do we want to expose that message to the end user? Darrell: should go into log and maybe also to user. Elaine: maybe could also say in the message that "some atoms are too close together" or "some atoms are too close too each other". Eric: I can upgrade this message about backtracking the bonds from an informational message to a warning message.

Scooter: we need to start thinking about the next round of the contract. What would be on your wish list?

• continuing support for NIH3D
• DICOM and segmentation (we now have a collaborator at UCSF)
• VR and interfaces in VR for DICOM or other applications
• what else?

Darrell: thanks for bringing this up. Yes we do want to continue, and I like those items. NIH3D is now officially running and in the public beta stage. We welcome any feedback you would be willing to give; Kristen can help to set up access. We like to make our pipelines public, put scripts on Github. Is there anything else we can do to share our work relating to ChimeraX? NIAID has its on internal app store, which includes licensed packages, and we would like to add the open source ones like ChimeraX. Can we add a ChimeraX install in our app store without your losing the download statistics? We have an app store for Mac and one for Windows, no Linux. Scooter: should be doable, if there is a simple way that we can make it clear that it cannot be shared to commercial users, and get the download statistics. Darrell: just the latest production release.

Phil: another idea we would like to add is getting a session of ChimeraX that can go to a Quest2 headset that is not connected.

Darrell: another idea is to explore the pedagogical benefits of ChimeraX in VR vs. laptop/desktop. Elaine: our group has not designed/conducted studies with human subjects (or any statistical studies, for that matter). Scooter: Kristen, maybe can use your bioviz lab for this study. What is the metric of comparison? Some kind of understanding or findings from the 3D structure. TomG: there are papers on studies on this topic for biomolecular visualization, which have not been very convincing. Phil: at least in ChimeraX, we can get a very similar scene, as opposed to comparing two completely different programs. Elaine: still the interfaces are quite different. Greg: also comparing with stereo would be a fairer comparison than with laptop/desktop screen. Scooter: but stereo is less and less available these days so it would not be an ultimately useful comparison.

Scooter: I will miss the next meeting, but please do continue to add or refine ideas for the next SOW.

12/8/2022

Phil, Kristen, Michal, Meghan; Eric, Elaine, TomG, Scooter, Zach

Kristen made tickets for several pipeline-stopping small-molecule CIF structures: was many before, but now only 10. If fixes won't be soon enough we can special-case the 10 out for now. Eric: Greg was in the middle of working on small-molecule CIFs. Some work, but some others may not. Eric: one current problem is an error in falling back to small-molecule CIF when the mmCIF reader falls. Unfortunately this is Greg's area and he may not be able to finish the fixes soon enough. Phil: we can special-case the 10 problem structures for now. Kristen: going forward, need to track the errors so that they can get fixed later. Plan for beta release is a restricted set of users for about 2 months (until approximately the end of February).

Another problem is "SDF: list index out of range". Eric: these files have a different type of line returns in the charge section (just carriage returns without newline). I can fix this specific error by looking for embedded carriage returns and doing an extra line-splitting step. But will other bad-format errors arise? Can't foresee them all... Kristen: we can raise a format error. Scooter: should reach out and find out if a commonly used program is generating this weird type of file. Kristen: OK we will reach out and get back to you.

Another problem: ValueError: all hydrogen names for /A NH2 37N taken. Eric: the NH2 capping residue is disconnected so it gets an extra hydrogen. Unfortunately it may be a Greg issue if the mmCIF reader is omitting a bond. Phil: the mmCIF file (biounit version from PDBe) just doesn't have the bond info, but Pymol adds it. Eric: maybe based on distance. #8139. Elaine and TomG: there are two biounit fetch sources, rcsb_bio and pdbe_bio and they are done differently. One uses multiple models and the other puts them all into one model with more chains. Eric: maybe script should just remove and re-add all bonds. It won't take long. Tried on example 2mag: ~bond #1; bond #1

Linux build broken since 12/6. TomG will try to fix today and comment on the ticket.

Another: NMR structure of DNA treated as small molecule. Eric: caused by assembly file again. TomG: this file (2miv) is weird, has multiple models with atoms for the various models interleaved in the atom_site table. Not sure this is allowed in the mmCIF format.

Another: need to decide on why the 500-atom criterion is in the ribbon preset, adjust it or remove it. Phil: couldn't come up with the rationale, maybe we should just remove it. TomG: or change behavior of "struts" wrt atom display, but probably better to remove the criterion first and see if that gives what you want. Phil: let's try that.

Another: white patches on surfaces? Eric: surface colors wrong next to hidden ligands, fixed in preset about a week ago.

Another: a case of coordination bonds in printed version being dashed, need to be solid. Eric: print presets already change pseudobonds to solid sticks, so need to send me the specific example. Phil: will doublecheck and let you know.

Meghan is in their viz space with giant screen. There will be classes, and groups can sign up to use the room. 98" 4K monitors, transparent film in doorway, 2 80" 8K monitors will be on opposite wall.

Next meeting? Should we try to meet earlier in the week since 12/22 is unlikely? We can wait until the new year, 4 weeks from today: Jan 5.

11/10/2022

Phil, Darrell; Eric, Elaine, Greg, TomG, Zach, TomF

Darrell: UC Budget office has not yet invoiced us for September or October. TomF: I will contact the office this afternoon and ask for it to be expedited. Darrell: Nada Midani is the contact on our side.

Phil: Kristen and Michal not here, too busy with NIH3D and didn't have any more questions/issues for you at UCSF. Phil: workflow is moving along, we are doing much more testing.

Usage question about ChimeraX from a structural biologist: how to turn on independent rotation? TomG: tile and ~tile automatically turn it on and off. Elaine: or if you don't want to change the current positions [put in chat]: mousemode left "rotate independent" and to put it back to default... mousemode left rotate

Phil: did Enduvo people ever get in touch? TomG: no.

Eric: there was one problem with pipeline hanging on charge calculation for a large "small" molecule. I suggested using Gasteiger instead of AM1-BCC. Phil: I thought the pipeline didn't show molecular surface ESP for small molecules. Eric: Kristen reported the problem, it was from PubChem. Phil: that should be an SDF file and not go through the surface representations. Eric: in that case we wouldn't need to worry about charge/Coulombic calculations for that structure. Darrell, Phil: we will investigate on our end and see whether that structure is going through the correct pipeline or not.

Eric: Add Charges tool available in today's daily build.

Phil: news on 1.5 release? TomG: a few more bugfixes to go, then a couple weeks after that. DICOM stuff, AlphaFold database version 4.

Phil: NIH3D timeline is "friends and family" release in December to get more outside testing, then advertising more broadly a month after that. TomF: which Linux are you running? Phil: not sure, can ask.

Eric: do you need the 1.5 release before your release? Phil: it would be nice but we can upgrade later if needed.

Next planned meeting will be in a month, but Phil et al. can contact us as needed in the meanwhile.

TomG: new command to run ESMFold or to fetch from their database.

10/27/2022

Phil, Kristen, Michal; Eric, Elaine, Greg, TomG, Zach

They are busy ramping up the 3D pipeline, Eric and other team members have already responded to and addressed several issues. Eric is testing a fix to the presets to handle grouped models (e.g. NMR ensembles).

Kristen: some workflows are hanging, maybe within a preset? Have been submitting ChimeraX tickets with long Log to help diagnose the problem.

Phil: have been asking about making ChimeraX read X3D; it currently exports that format but does not read/display it. Greg: not impossible but would take a lot of work; perhaps easier would be reading the VRML subset, but even that would take some time. Elaine: didn't Chimera include an x3d2vrml script? Would that help? Greg: maybe; worth trying.

Phil: have been using 3dqsar.com that does CoMFA (comparative molecular field analysis) now that the Tripos patent exclusivity has ended. Can output cube files and display in ChimeraX, which is nice.

Phil: may consider adding reading VRML to ChimeraX as a goal in our next contract. Greg: reading small molecule CIF could be another feature to add to a future contract. Maybe you can use openBabel to convert small molecule CIF into SDF.

Phil: any updates on the timing of the 1.5 release? TomG: we estimate at least 2 weeks away, as various bug reports have come in since the candidate.

Kirsten: we are trying to get from GLB with textures to X3D with textures. We have lots of fancy GLB with animations, etc.

Phil: what about DAE? Elaine: currently ChimeraX can read it but not write it. TomG: we could add writing DAE; we had concentrated on GLB. Kristen: writing DAE would be useful. We do need GLB for web, so it was not a mistake to prioritize it.

Phil: what about FBX? Kristen: proprietary, owned by Maya.

Discussion of VR latency when using cloud service. TomG: probably would not work well in many cases. Many may prefer to use Nanome (standalone) and leave ChimeraX out of the equation. Phil: prefer ChimeraX for cases where you want to go in and out of VR, using desktop part of the time.

10/13/2022

Phil, Kristen, Michal, Meghan; Eric, Elaine, Greg, TomG, Zach

Phil: It's crunch time for NIH3D. Kristen has two questions...

Kristen: re presets, we are missing output for rainbow-vis, ribbon-bychain-vis, ribbon-secondary-vis. Phil: these presets are in the menu, they just aren't named with "vis." Kristen: we are getting outputs for the printable versions but not the visualization versions. Eric: I will fix the script to also generate outputs for those. Phil: the presets exist. Michal: These are updates to the scripts rather than the presets themselves.

...at end of meeting: Michal: I think I made the needed changes, Eric should check.

Kristen: we also want to synchronize with your ChimeraX 1.5 release. What is the timeframe? TomG: release candidate starting today, typically wait 2 weeks to a month to make it official. So a rough estimate is mid-November. but it really depends on the bug reports that come in. Phil: so we should get the release candidate. Kristen: will we be notified automatically when it's available? ChimeraX team: we don't email the whole list for the candidate but we can email NIAID folks about it. TomG: typically release about twice a year.

Kristen: we need to release NIH3D by December.

What's new: dockprep command, axes/planes/centroids, MOLEonline reader, ...

TomG: would it be useful to be able to color the channel by properties? Phil: yes our collaborator was interested in something like that, although we did not discuss details. The mutation of interest changed the pore. Elaine: probably more interesting/helpful to show surface of marker model and then color by protein's ESP or MLP.

Phil: the HOLE results looked better because the surface was smoother (planes and resulting spheres closer together). TomG: molecular surface on marker model would also help take care of that.

TomG: been doing more VR recently. New more expensive Quest system has been announced, not sure we need any of its latest features. Have experimented with using OpenXR instead of SteamVR. Phil: does it work with Macs? TomG: Not as far as I know. Rumor is that Apple will release a headset next year.

Phil: now in Meta store, Dlink VR Airbridge, ~$100, dongle with built-in router, supported directly by Quest2. Victor just ordered a couple for us to try. Unclear how many can be used in the same room.

Meghan: we are excited to finally have access to our new bioviz lab, after county inspections etc. Still trying to catch up after the trip. AR/XR Nigeria involved some medical students, there is a lot to follow up on. Need to find private partner for $$ support for their activities. Have been in contact with Meta. Phil: training courses for hackathon prep will include VR basics, Unity. That was funded by Meta. TomG: we have funding from CZI for software maintenance.

Discussion of rollout of new NIH3D. Old one is running older software that won't get security updates after November; although it won't be shut down until somebody tells us we have to shut it down, that's one important reason we want the new one to be available in December.

9/29/2022

Phil, Darrell, Meghan; Eric, Elaine, Greg, TomG, Zach, Scooter (briefly)

Zach has progress on DICOM, will put in daily build soon:

• Model panel shows hierarchy as Patient, Study, Image (series), and there will be a new DICOM browser and metadata browser (shows demo on his screen). Meghan and Phil: nice job! Phil: do you anonymize the data? Zach: we don't, so far have only dealt with data already anonymized. Meghan: the DICOM browser is very helpful when multiple series are in the folder. Eric: is that dialog shown in VR? TomG: yes.

Elaine: maybe people would mostly use the DICOM browser to understand the data and decide on the series of interest before going into VR.

• Also have found and met with local collaborators who work with medical imaging and are interested in 3D applications. Phil: I would be interested in further developments for segmentation in VR, are they interested in that? TomG: one of the collaborators does segmentations and we will be viewing that in VR. Collaborators are Jason Crane, Vanitha Sankaranarayanan; they showed Tom and Zach a video of liver segmentation by Jesse Courtier (at Mission Bay, also interested in collaboration): ​https://www.youtube.com/watch?v=Dy5h1482IzY
• next steps are to polish up UI, meet with Vanitha et al., elicit feedback on interactions in VR
• Eric mentioned our argument in group meeting earlier today about extracting all of DICOM functionality into a bundle or not; they see pros and cons, but Darrell agrees with Elaine about keeping some DICOM functionality in the download for findability (which has implications for the broader issues of accessibility and pedagogical utility). Meghan: yes, having to explain two installations rather than one really increases the barrier to use in a classroom environment. TomG: this discussion came up because we would need a large package GDCM to read a specific format (lossless 16-bit JPEG that we cannot read currently)

Phil: when your system was down, pipeline got stalled because it was trying to fetch presets from toolshed. Eric: they should not be doing that every time it is used. They should install the wheel and only update it when an update is specifically available. Or, if they are creating a new virtual machine each time, they should cache the wheel locally and keep reusing it. Eric: we also had a problem with slow startup when ChimeraX was trying to check the toolshed. There is a ticket: #7659. Greg: it only affects interactive use, however, not running in nogui mode.

TomG was working late last night trying to get better performance from the Quest2. (We want to get a Quest Pro as soon as they are available.) Better when set to 90 fps instead of 72, unclear why. Darrell: 72 is probably the default to prolong battery life. TomG: maybe SteamVR apps are optimized for 90. There's a huge number of possible combinations of settings, and most of them don't work that well.

Elaine: what about Africa? Meghan: Phil did a workshop with students who were very enthusiastic. It went quite well, would have liked one more day there. Phil: we spent time making and manipulating structures in ChimeraX, ending up with them viewing the structures in VR. It was hard to get them to stop, and more students than headsets. US ambassador to Uganda was also there, and Christian Hapi who wants to build a VR lab and may have been more excited than even the kids. Ugandan embassy press release: ​https://ug.usembassy.gov/african-centers-of-excellence-in-bioinformatics-and-data-intensive-science-2022-annual-consortium-meeting-student-showcase-september-13-2022/ Darrell: we've really been using ChimeraX a lot there, and it was surprising that the ambassador stayed 2 1/2 hours! Darrell: one reason for this outreach is to promote infectious disease research worldwide rather than trying to fight diseases only from home.

TomG: must be harder in Mali where French is spoken more than English. Darrell: definitely, but English is the primary language of science these days.

Phil: I have to remind myself to talk very slowly in Mali. As an example of trying to accommodate both French and English speakers, there will be a VR hackathon in Africa presented in both. Darrell, TomG: maybe we can try to develop a French version of a tutorial.

Phil: TomG, I still want to put you in touch with Enduvo developers (CEO Justin ? was also in this Uganda meeting). There were poster sessions in Africa and one student developed her "poster" with Enduvo in VR. We had to use a Blender script to convert colors, combine objects, etc. so there are a lot of steps between ChimeraX and Enduvo that we would like to streamline. TomG: texture colors option should work, but I haven't been able to get a copy of Enduvo to test with yet.

9/1/2022

Phil, Michal, Nada Midani (at beginning); Eric, Elaine, Greg, TomG

Nada: please do submit your paperwork soon. Elaine: we did update the document already, but Scooter knows how to submit it, would next Mon/Tues (when he returns from vacation) be OK? Nada: sure, that would be fine. (later: oops Monday is a holiday, but Nada had indicated by Friday at the latest would be acceptable)

(ChimeraX team introduces themselves to Nada and she signs off)

Phil: Michal, do you need anything from the ChimeraX team for NIH3D at this point? Michal: no, nothing to ask now, since I've been working on other aspects and other projects lately. Phil: including the metadata like atomic weights. Michal: yes, I think we accomplished everything requested so far.

TomG: is there an ETA for the new NIH3D website? Michal: dev version is being tested but not yet public, plan is for public release in December. We stopped always using latest daily build, now we just get new ChimeraX periodically by hand. TomG: what OS will be running? Michal: Ubuntu 20.4.

9/15 meeting is canceled since they'll be en route returning from Africa. Next meeting 9/29.

African collabs using Enduvo, so much of the work is getting ChimeraX GLB into that program. Currently gives error on import "not fully supported," recommends using gltf version 2.0. TomG: I thought that's what we were producing. Greg: is it something about texture coloring? Phil: surface colors are showing in Enduvo but not ribbon/atom colors, which are shown as white. TomG: maybe our single coloring such as used for atoms is not recognized. May need to use per-vertex colors instead. TomG: do they offer a free trial so we can try it? Have you noticed other problems besides color? Phil: no.

Phil: another collaborator wants to make an image with something like HOLE. Elaine: unfortunately Chimera/X doesn't have a builtin feature like that. Eric: there is a MOLE plugin for Chimera, see plugins page. Elaine: There's a MoleOnline server that makes output for Chimera Moleonline server ​https://mole.upol.cz/ Moleonline image from Chimera ​https://www.rbvi.ucsf.edu/chimera/related/mole1bl8.png

Eric: latest update is that there is a dockprep command. Phil: how do you parametrize ligands? Elaine/Eric: Ambertools 20 Antechamber, GAFF types and choice of Gasteiger or AM1-BCC charge calculation.

TomG: cryoDRGN is an AI program to figure out heterogeneity in EM data. Just started adding a tool in ChimeraX to look at the output. It's in R01 proposal but we don't know for sure whether the renewal will be funded or for how much, maybe will find out by the end of the year. (shares screen showing clicking on the UMAP and displaying the corresponding density map)

TomG: soon I plan to work on making a "laser pointer" within VR

Phil: when we get back from Uganda, plan to try using multiple Quests at the same time in the VR lab

8/18/2022

Phil, Darrell (at end); Zach, Eric, Elaine, Greg, TomF

Phil: going to Uganda (along with Darrell and Meghan) in a few weeks, would like to show VR, and any new stuff with DICOM. Will be here for our next meeting (9/1), but gone for the one after that.

Zach: have been refactoring DICOM bundle, have been working on a DICOM browser to show the hierarchy with option to show full metadata. We have reached out to local radiologist, trying to set up a meeting to show in VR, but not done yet.

Phil: NIH3D any recent issues? Eric: haven't heard from Michal since last meeting. Elaine: we've been working on axes/planes/centroids. Eric: and Dock Prep, but still not done.

Elaine: do you (or NIH3D) represent the membrane? Could get the PDB from the OPM (orientation of proteins in membranes) database, which represents the membrane as a bunch of singleton atoms in a plane. I can send an example or two using "define plane" and/or "molmap" to make those atoms into solid surfaces.

Phil: my other question was for TomG, but I'll ask anyway... files from alphafold get saved in downloads but folders are just named prediction_1, prediction_2. Would like to get a more descriptive folder name so it would be easier to tell which modeling job was which. [shares screen] especially when I click Error Plot and get a dialog asking for the location of the file -- I don't know which one will go with the structure. Would be nice if it asked for a job name beforehand, say when you click Predict, and then name the folder with that. Elaine: I will make a ticket and put you as the reporter.

Darrell: next meeting, I invited Nada Midani, program manager. TomF: unfortunately Scooter will not be here. Darrell: maybe will have to wait until later in September for Nada to meet Scooter. Phil: we will still have a meeting 9/1.

Darrell: two quick questions. (1) is alphafold db version 3 hooked up to ChimeraX? Elaine: yes, may need daily build, see "version" option of alphafold fetch and alphafold search. (2) ChimeraX use for cryoET? yes, we see several citations, and there is a new amazing huge bundle for working with cryoET on the Toolshed now, ArtiaX. TomF: and they have documentation!

8/4/2022

Phil, Meghan, Michal, Darrell, Philip; Zach, Eric, Elaine, TomG, Greg, Scooter

Phil: what's going on with ChimeraX scripts for NIH3D? Michal: I deployed the presets with help from Eric, and used ChimeraX to report voxel size. That's everything on our list for now.

TomG: saw check-ins related to DICOM in pipeline code, are there issues we can help with? Michal: not that I know of, got pixel spacing, and will let you know if other issues arise. Scooter and Zach are setting up meetings with some UCSF radiology folks to get feedback on visualizing medical images.

Meghan, Phil: would be interested if they have any feedback on NIH3D as well, and if they're using AR/VR. Meghan: we had visitors using AR, Hololens 2. TomG: we don't have a Hololens, would be interested in trying molecular data. Phil: we were working with a company Enklu to put a molecule in a scene for the Hololens 2. Static model was fine but trying to move it was very stuttery. Could have been due to the overhead of the Enklu environment. Meghan: it was "no code" but had a rather high learning curve. One limitation of Hololens is restricted field of view. Phil: had to play around with room lighting to see model clearly, rather than washed out. Scooter: they are relatively expensive. TomG: AR seems good for Jacobson group use case, where people discuss a few different structures without a lot of VR manipulation.

From Zoom chat:

• Darrell: AR company I recently found out about: ​https://varjo.com/products/xr-3/
• Meghan: see ​https://varjo.com/products/xr-3/

Meghan: we will be setting up a lot of hardware in Uganda, need to get more base stations. They keep failing, maybe were kept turned on continuously for too long. Even a used one is $270 on Amazon. Darrell: maybe should get on/off switch. TomG: maybe is better to leave them on rather than a lot of power cycling. But dust, power surges, temp fluctuations could all help to do them in. There are other ways to turn off, say via SteamVR.

ChimeraX stuff. Eric: there is a Change Chain ID tool. Have made progress on Dock Prep, but it's very complicated and not there yet. Could be a couple more months. Scooter: we are thinking about what features should be in version 1.5.

TomG: Latest AlphaFold DB release has >200 million structures. Can fetch a specific ID quickly but searching all the sequences takes a while. Looking at RNA model database, and another method, Esmfold ​https://chowdera.com/2022/207/202207262300487520.html\

Elaine: this paper presents AlphaFold2 performance on cryoEM challenge datasets ​https://www.sciencedirect.com/science/article/pii/S2589004222007672

Meghan: we're also thinking about network visualization tools for our Uganda collaborations. Maybe something along these lines could be included in our next contract.

7/7/2022

Phil, Meghan (last part); Zach, Eric, Elaine, TomG, Scooter

Phil: status of presets bundle? Eric: bundle is on toolshed, gave Michal a workaround to get it working, but haven't heard back

TomG: M1 build should be available sometime next week, pending Riverbank (Phil Thomson?) getting the PyQt commercial wheels working on M1. We will put it on the download page.

Eric and Elaine: Renumber residues command and GUI are in the daily build, change chain ID command tomorrow, GUI also should be done in a day or two. Phil: very happy to see this, one of the few remaining reasons I go back to Chimera. Is there a GUI for Color Secondary structure? Elaine: not currently... we figured the 3 commands were not hard (color helix purple, etc.). Scooter & Eric will add to list of requests.

Phil: another request is related to the AlphaFold PAE plots. Default for alphafold fetch is trim true, but then can't get PAE plot. Must re-fetch with trim false. Maybe add option to GUI for fetch w/o trim. TomG: another possibility is to make it smarter to work after trimming. Have considered some alternatives, but there are potential pitfalls. Elaine: what about trim false? TomG: trim true is a better default for alphafold match. Phil: having it work with trimmed structures would be the best.

TomG: have you tried displaying the pseudobonds colored by PAE values (alphafold contacts)? Phil: not yet, but I remember you showed it. Phil: another hangup remembering the right option to get the pkl file (with PAE plot info) monomer predictions.

Phil: having difficulties reading mmCIF headers to get metadata, any pointers? Some types of information can be in multiple different places, depending on the specific file -- not predictable/consistent. TomG: Greg (on vacation) is our main mmCIF guy, but I've written code to obtain specific information like UniProt IDs from those headers. TomG: recommend complaining to RCSB PDB helpdesk when the info (EMDB code or whatever) is missing from what the REST service returns. Scooter: So far, I'm consistently seeing the EMDB codes in _database_2.database_code (and then *sometimes*) in some of the other fields. Eric: can use graphql to get the information instead of getting the whole header from RCSB PDB. You can get it for multiple entries at once, returns json. Our tool showing BLAST results uses graphql.

TomG: have been looking into ColabFold -- significantly faster and may have other advantages (use of template structures?). Need to ask authors if it's OK for ChimeraX to interface with their server.

Meghan: Meta changed policy, won't need a Facebook account for the VR stuff. We'll be going to Uganda in the fall.

6/9/2022

Phil, Philip, Michal Stolarczyk and David Liou from 3D pipeline team, Meghan (last half); Zach, Eric, Elaine, Greg, TomG, Scooter

Self-introductions from both teams.

Michal is currently the primary developer working on NIH3D, working for last month on infrastructure. ChimeraX script has been running without issues, so he hasn't been working on that part. ~10-min slide presentation.

Running Ubuntu 20.4 0 within EC2 instance within VPC within AWS. Involves Prefect and GraphQL.

Recent updates:

• workflow deployment: standardized flow names, external Postgres database
• workflow handling: ​https://niaid.github.io/nih_3D_workflows, JSON-based configuration

Planned enhancements:

• switch to ECS for running flows (to handle more at the same time)
• increase reproducibility of results by including code versioning
• use newer version of NIH3D presets provided by Eric

Phil: Eric please explain unified script and presets

Eric: originally all the types of view/displays that could be requested by the user were in a giant script with lots of commands, and we decided to refactor that as a set of presets where each preset generates one type of view. Now a smaller script calls the individual presets as needed. This set of presets is available as a bundle on the ChimeraX toolshed. Would have to re-install if ChimeraX is not persistent between runs.

Michal: ChimeraX is persistent on the same machine, but different machines are used. When we use ECS it will deploy a docker image that could have the bundle already installed.

Eric: how long to deal with my pull request? Michal: about a couple of weeks.

Eric: ChimeraX now has "renumber" command, on the way towards having a GUI to do it.

Some discussion of reproducibility, ChimeraX preferences and fetch caching.

Phil: are ChimeraX-calculated values saved somehow? Eric: currently, the script sends them to standard-out with a standardized prefix to facilitate grepping the lines. Could be changed if needed.

TomG: new "alphafold contacts" command to draw pseudobonds as explained in https://www.rbvi.ucsf.edu/chimerax/data/alphafold-contacts-jun2022/afcontacts.html

Phil: what about similar pseudobonds for contacts? Elaine: can be done with "contacts" command but we don't have anything to color them continuously by length yet. Scooter: might be interesting to show histogram by length with "crosslinks histogram". Elaine: clicking a histogram bar interacts with corresponding pseudobonds.

Zach: has reached out to Jason Rubinstein, he will take a look at his data using our latest DICOM/VR and get back to us

Meghan: we still need to give feedback on where the buttons are on different VR hand-controllers, for better mapping to the cone display in the headset. TomG: we currently use two different layouts, one for Vive and one for Oculus Rift. So more could be added.

5/26/2022

Phil, Philip, Darrell (Meghan sick today); Zach, Eric, Elaine, Greg, TomG, Scooter

Presentation by new NIH3D workflow developer, Michal? Not scheduled yet, maybe next time. Phil: will see if he's available to join this meeting. Phil: have done a little testing on the latest bundle from the toolshed, will send (minor) comments via e-mail. Main issue this week was NIH3D pipeline breaking due to changes in metadata, but has been dealt with. Darrell: was not related to Chimera, was caused by a change in the XML from EMDB.

Darrell: how can we get an approximate contour level if we fail to get one from EMDB? Eric: there is already some iterative process to setting a contour level that makes a coherent blob. Darrell: sounds good.

Darrell: we would like TomG to come to Wash DC and also Rocky Mtn Labs. Scooter: we budgeted for those two trips. Phil: maybe for the Biovis lab opening events. Darrell: time frame is uncertain, originally planned for fall but there are many other important meetings at about the same time, so it may be delayed. Darrell: will be going to Nigeria for an NIH meeting (the last "H3" meeting; had demoed VR there in 2018). VR demo has been requested for a meeting in Mali, at rather short notice. Phil: there was a VR-collab demo between Mali and Uganda not long ago.

Darrell: what systems are good to show in VR? Phil: TB drug resistance. Is this a demo? Darrell: maybe a video but not by this Sunday when they wanted.

Phil: I've been trying the release candidate from 5/20, haven't found problems.

Darrell: do you have an M1 version? Zach: In progress. Elaine: I've been using the existing download (via emulation) on an M1 machine without problems, works well. Phil: everything seems twice as fast, even with the emulation, on my M1 machine.

TomG: CPU speed on M1 is great. I made a benchmark page https://www.rbvi.ucsf.edu/chimerax/data/czi-nov2021/apple_m1.html

Philip: what are the Rocky Mountain cluster. Darrell: GPUs are the one before A100, something starting with a different letter. Scooter: We are using A40 and A100 on our cluster.

Scooter: would like to discuss DICOM at a later meeting. Elaine: are we hearing from Michal next time? Phil: I'll check with him and get back to you.

Darrell: Brad and Ziv may be able to provide datasets. Scooter: maybe we can also get them to join the discussion. Elaine: to say how they analyze the data. Darrell: focus on visualization component, not to replace these other packages like Slicer3D. Phil: maybe some analyses would be great to combine with VR. Darrell: maybe should get Dave (he's responsible for the Visible Human stuff) to present as well. How about we get them to view DICOM in ChimeraX and give comments? Scooter: that would be good, too. TomG: we need a VR-specific perspective, though. Scooter: maybe NIH folks can set up a DICOM-VR session. Phil: maybe Dave + TomG in VR meeting. TomG: sounds OK, but I still think that we need to get more feedback from Jason Rubinstein (or other people that really work with both medical imaging and VR). Remote meetings have limitations, however; talking face-to-face in the same room is really the best if possible, say during my visits. Darrell: then maybe Jeff Solomon, perhaps NIAID's most DICOM-oriented scientist. Dave certainly knows DICOM, too. Maybe we could fly Jason Rubinstein in from Wisconsin. TomG: can we afford to fly Zach in too? Scooter: currently contract has 2 trips for one person. Darrell: maybe we can find additional funding.

5/12/2022

Phil, Philip, Meghan; Elaine, Eric, Zach, Greg, Scooter

Scooter: we are planning a group off-site get-together, maybe October, maybe sailing.

Scooter: contract agreement is done! Tom G is the unofficial lead on this NIAID funding, but he's on vacation now, so we don't have much to say yet. Zach will be working on the DICOM stuff. Status of NIH 3D?

Phil: last I recall, still waiting on progress with the workflow server to handle new submission process and use of presets. Eric & Greg worked out the toolshed issue, and the bundle is available there. Philip got called to another project and another developer (Mihal?) is taking over the NIH 3D workflow programming. Kristin is now the development coordinator for NIH3D.

Scooter: maybe that person can present at our next meeting? Meghan & Phil agree. Meghan will ask Mihal about doing this.

Scooter: progress on AlphaFold but we would also like to look into RosettaFold calculations too. Phil: RosettaFold is harder to use. It was also reasonable to start with AlphaFold since EBI is providing a database of already-calculated models. Scooter: there was some talk of RCSB starting a RosettaFold database.

Scooter: Elaine's been presenting DICOM and DICOM viewers, and we have a couple of possible people to work with for real data & applications, Jason Rubenstein at Medical College of Wisconsin, and previously there was somebody else in South America. Of course we still want to hear any requests or suggestions your group has for DICOM in VR, which would be top priority for this contract.

Meghan: we've had a lot going on, not to mention the pandemic disruptions, so we need to revisit VR medical applications along with our collaborators in Uganda. We're meeting with them in a couple of weeks. We're also working with other groups in VR medical applications (NHS in UK for health training) and come up with our next strategy and get back to you later. I'm glad this is back on the radar! We will also be getting more hardware.

Scooter: we have a good wifi setup for untethered Quest headset now. Required wrangling with UC IT to allow setting up our own wifi6 router (?) only for this limited purpose. Campus wireless was unusable for this purpose.

Phil: in ChimeraX, a big advantage is that we can go inside models in VR. Medical Holodeck doesn't really allow this, framerate goes way down. Meghan: Medical Holodeck is just too heavyweight for convenient use in many situations.

Phil: we like that the mapping of buttons to the cones shown in VR. However, the mapping is not good for some of the controllers where the buttons are in different places. So we would like Tom G to take a look at making different mappings that better match the different controllers. Elaine: I'll make a ticket and maybe Phil can add comments about which ones are mismatched.

Phil, Meghan: Another recent problem with old (Chimera) pipeline may be related to EMDB metadata. Eric: new (ChimeraX) pipeline gets recommended contour level; don't know what the old pipeline does. Phil: I think the problem is not in Chimera but in some other step.

Scooter: 1.4 release is coming soon, release candidate is available.

4/14/2022

Phil, Philip; Elaine, Eric, TomG, Zach, Greg

Today Darrell authorized "MSC" (or logical equivalent) to act on UCSF’s final proposal against the SOW!

Phil: I hear that the new NIH3D workflow will be deployed soon. Kristin will be project coordinator, maybe she will attend some of our meetings in the future.

Phil: Eric, please add the GLTF (glb) saving option "center 0,0,0" to the workflow. TomG: don't bother, I'll make that the default.

Eric: I still can't upload the bundle to the toolshed, because... Greg: dependency field issue with comma in string. Will be solved by upgrading to newer mariadb, should be done within a week.

Eric is working on joining models, starting with peptide bond.

Phil: gave a talk to the structural biology group, showed alphafold PAE plots -- people were very interested and liked the ability to switch between domain and confidence (pLDDT) colorings. Elaine: there's a Youtube video of TomG's recent SBGrid workshop on that topic.

TomG: maybe we can also color by conservation calculated from the giant sequence alignment alphafold uses to covariance.

Phil: people had several suggestions: (1) to predict every chain in an existing PDB. TomG: you can do that now, just open that structure first and use "alphafold match" ... however, what you get may have a different albeit similar sequence (top BLAT hit) (2) another request was to draw chain boundaries on the PAE plot for the multichain case. (3) for selected residue, color others by their PAE with the selected residue. Could also color-code pseudobonds, or only draw pseudobonds for certain range of PAE values. (4) report X,Y cursor location when over the plot (e.g. residue numbers, chain IDs) TomG: what about on the structure? select the 2 residues? draw a pseudobond between them? (5) allow zooming in to regions within the plot

Phil: does predicting in ChimeraX work with a user's Colab Pro or Pro+ plan? TomG: yes, since you sign in to Google it knows you have an account.

TomG: do you have any experience with Vive focus 3? Phil: we may be getting one soon, as well as HP Reverb and Pico (sp?), which has eye tracking... the hot new headsets. Will let you know. TomG: I like the Vive pro 2, higher resolution, eye tracking.

3/31/2022

Phil, Philip; Elaine, Eric, TomG, Zach, Greg

Status of SOW? Still being negotiated. Phil: what is highest priority? TomG: We're told it won't start until May 1, so we haven't thought mcuh about it yet. The SOW includes machine learning & AlphaFold stuff. Phil: everybody's interested in using that now. TomG: shows AlphaFold "predicted aligned error" (PAE) plot just added to ChimeraX. Google Colab version doesn't use templates, so PAE domain identification is based on residue covariance. PAE plot and interaction with structure in ChimeraX is similar to that available at the AlphaFold Database, except the ChimeraX one is better if you highlight an off-diagonal box on the plot (shows 2 colors on structure).

Discussion of importance/predominance of disordered regions in proteins. Phil: simulations don't model these well.

Phil used to work at Tripos. Elaine: my first modeling work was with SYBYL (from Tripos) on the Evans & Sutherland! Phil: booting up the E & S took forever.

TomG: I added a tug command to fix up linkers after building a large, complicated protein structure.

Elaine: figured out how to show time series in 3D Slicer. At least some of the problem was due to the version of 3D Slicer - time series example files for one version don't work in the other (without additional steps needed to define a set of maps as a time series).

TomG: looked at the NIAID TB-VR experience website, sent feedback to Phil. Phil: here's the URL, public now: ​https://tbportals.niaid.nih.gov/tb-in-vr TomG: "save" GLTF has a "center" option. Maybe we should make the default "center 0,0,0" ... downside is when the user wants to preserve the relative locations of multiple structures.