James Fraser
@fraserlab.com
Professor and Chair @UCSF/@UCSF_BTS - dynamic structural biology and open science - (he/him) - fraserlab.com
🤯
New Preprint!! We show that binding entropy can be quantitatively predicted from crystallographic ensemble models, accounting for both protein conformational entropy and solvent entropy! www.biorxiv.org/content/10.6...
January 21, 2026 at 10:08 PM
🤯
Reposted by James Fraser
New Preprint!! We show that binding entropy can be quantitatively predicted from crystallographic ensemble models, accounting for both protein conformational entropy and solvent entropy! www.biorxiv.org/content/10.6...
January 21, 2026 at 8:49 PM
New Preprint!! We show that binding entropy can be quantitatively predicted from crystallographic ensemble models, accounting for both protein conformational entropy and solvent entropy! www.biorxiv.org/content/10.6...
Reposted by James Fraser
A recent podcast by Stephanie Wankowicz and James @fraserlab.com picked up our work (with Alex Bronstein & coworkers) on Guiding AlphaFold3 with experimental data (cryoEM, X-ray, NMR) to generate protein ensembles. (Thanks for the kind words 🙂)
👉 creators.spotify.com/pod/profile/... (from 35:50)
👉 creators.spotify.com/pod/profile/... (from 35:50)
Episode 8: Open Science in a Changing Academic World by The Tortured Proteins Department
Topics:Compact for Academic Excellence in Higher EducationGovernment ShutdownHHMI's new open science policiesShrinking PhD poolsThe Nobel PrizesThe BearTLOS ReactionsPreprint: Experiment-guided AlphaF...
creators.spotify.com
January 21, 2026 at 2:14 PM
A recent podcast by Stephanie Wankowicz and James @fraserlab.com picked up our work (with Alex Bronstein & coworkers) on Guiding AlphaFold3 with experimental data (cryoEM, X-ray, NMR) to generate protein ensembles. (Thanks for the kind words 🙂)
👉 creators.spotify.com/pod/profile/... (from 35:50)
👉 creators.spotify.com/pod/profile/... (from 35:50)
Reposted by James Fraser
As soon as NIH decided that preprints were A-OK we started preprinting everything.
The biggest negative is that now once we've preprinted I lose interest in the actual peer-reviewed article. Which for me isn't a big deal (I'm tenured) but my folk aren't. So I need to force myself to keep up on it
The biggest negative is that now once we've preprinted I lose interest in the actual peer-reviewed article. Which for me isn't a big deal (I'm tenured) but my folk aren't. So I need to force myself to keep up on it
January 12, 2026 at 8:25 PM
As soon as NIH decided that preprints were A-OK we started preprinting everything.
The biggest negative is that now once we've preprinted I lose interest in the actual peer-reviewed article. Which for me isn't a big deal (I'm tenured) but my folk aren't. So I need to force myself to keep up on it
The biggest negative is that now once we've preprinted I lose interest in the actual peer-reviewed article. Which for me isn't a big deal (I'm tenured) but my folk aren't. So I need to force myself to keep up on it
Reposted by James Fraser
Happy new year #teamtomo! We've resumed our OHSU tomo journal club, and this year I am going to be sharing it on bluesky. This week we did a roundtable, where attendees each brought a paper and did a 3-5 minute discussion of what they thought was cool about it. Here are the papers they discussed!
January 8, 2026 at 8:00 PM
Happy new year #teamtomo! We've resumed our OHSU tomo journal club, and this year I am going to be sharing it on bluesky. This week we did a roundtable, where attendees each brought a paper and did a 3-5 minute discussion of what they thought was cool about it. Here are the papers they discussed!
A reverse K99 would be interesting...
2 or 3 years of R01 type funding to wind down followed by 2-3 years of funding for supplies as you are hosted as an emeritus professor - and ineligible for future grants as a PI
2 or 3 years of R01 type funding to wind down followed by 2-3 years of funding for supplies as you are hosted as an emeritus professor - and ineligible for future grants as a PI
My postdoc advisor is an advocate for the “post faculty fellow” positions and in theory it sounds like a super cool idea.
That being said if anyone is wanting to do one in my lab, Please email me a CV and cover letter.
That being said if anyone is wanting to do one in my lab, Please email me a CV and cover letter.
Jonathan Hodgkin retired a while ago, and is working at the bench as an emeritus fellow in his former trainee's lab
January 7, 2026 at 4:41 PM
A reverse K99 would be interesting...
2 or 3 years of R01 type funding to wind down followed by 2-3 years of funding for supplies as you are hosted as an emeritus professor - and ineligible for future grants as a PI
2 or 3 years of R01 type funding to wind down followed by 2-3 years of funding for supplies as you are hosted as an emeritus professor - and ineligible for future grants as a PI
Reposted by James Fraser
What an extraordinary joy it is to finally be able to share this work with the world. If any of you are excited by chemoproteomics or new tools on the covalent warhead toolbox I think this paper may be right up your alley 💕
Is arginine the new cysteine?! Check out our lab's latest in collaboration with @ianseiple.bsky.social's team where we introduce ninhydrin as a selective covalent warhead and probe targeting reactive arginines.
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
Ninhydrin as a covalent warhead for chemical proteomic-enabled discovery and selective engagement of reactive arginines
Covalent molecules have emerged as next-generation therapeutics and as powerful tools for perturbing fundamental biological processes. Chemical proteomic methods to screen for reactive proteinaceous a...
www.biorxiv.org
January 6, 2026 at 5:28 PM
What an extraordinary joy it is to finally be able to share this work with the world. If any of you are excited by chemoproteomics or new tools on the covalent warhead toolbox I think this paper may be right up your alley 💕
Yes. This is a problem!
fraserlab.com/2025/09/08/N...
@prereview.bsky.social @richardsever.bsky.social
fraserlab.com/2025/09/08/N...
@prereview.bsky.social @richardsever.bsky.social
January 5, 2026 at 2:52 PM
Yes. This is a problem!
fraserlab.com/2025/09/08/N...
@prereview.bsky.social @richardsever.bsky.social
fraserlab.com/2025/09/08/N...
@prereview.bsky.social @richardsever.bsky.social
Reposted by James Fraser
I personally favor the notion "peer-reviewed" just means a paper with peer reviews, as opposed to a paper that's deemed to have passed some (ill) defined bar as a result. But I'm skeptical the community will embrace that - and even if it does I suspect they'll want curation steps with bars. 5/n
January 3, 2026 at 4:42 PM
I personally favor the notion "peer-reviewed" just means a paper with peer reviews, as opposed to a paper that's deemed to have passed some (ill) defined bar as a result. But I'm skeptical the community will embrace that - and even if it does I suspect they'll want curation steps with bars. 5/n
Nice to see an acknowledgement (and citation!) of our @prereview.bsky.social in the final version of this awesome paper (www.nature.com/articles/s41...) from @pilarcossio.bsky.social @sonyahanson.bsky.social investigating the promise and limitations of conformational heterogeneity analyses in CryoEM
December 31, 2025 at 6:32 PM
Nice to see an acknowledgement (and citation!) of our @prereview.bsky.social in the final version of this awesome paper (www.nature.com/articles/s41...) from @pilarcossio.bsky.social @sonyahanson.bsky.social investigating the promise and limitations of conformational heterogeneity analyses in CryoEM
And if collecting and analyzing X-ray structures at scale like this are your thing (or if you want to make it your thing), reach out!
We are recruiting at the postdoc or staff scientist level
Work on fun targets in the drug discovery/anti-target or neuro space!
We are recruiting at the postdoc or staff scientist level
Work on fun targets in the drug discovery/anti-target or neuro space!
I'm really excited to break up the holiday relaxation time with a new preprint that benchmarks AlphaFold3 (AF3)/“co-folding” methods with 2 new stringent performance tests.
Thread below - but first some links:
A longer take:
fraserlab.com/2025/12/29/k...
Preprint:
www.biorxiv.org/content/10.6...
Thread below - but first some links:
A longer take:
fraserlab.com/2025/12/29/k...
Preprint:
www.biorxiv.org/content/10.6...
Know when to co-fold'em
This is the official web page for the James Fraser Lab at UCSF.
fraserlab.com
December 30, 2025 at 4:07 PM
And if collecting and analyzing X-ray structures at scale like this are your thing (or if you want to make it your thing), reach out!
We are recruiting at the postdoc or staff scientist level
Work on fun targets in the drug discovery/anti-target or neuro space!
We are recruiting at the postdoc or staff scientist level
Work on fun targets in the drug discovery/anti-target or neuro space!
I'm really excited to break up the holiday relaxation time with a new preprint that benchmarks AlphaFold3 (AF3)/“co-folding” methods with 2 new stringent performance tests.
Thread below - but first some links:
A longer take:
fraserlab.com/2025/12/29/k...
Preprint:
www.biorxiv.org/content/10.6...
Thread below - but first some links:
A longer take:
fraserlab.com/2025/12/29/k...
Preprint:
www.biorxiv.org/content/10.6...
Know when to co-fold'em
This is the official web page for the James Fraser Lab at UCSF.
fraserlab.com
December 29, 2025 at 10:25 PM
I'm really excited to break up the holiday relaxation time with a new preprint that benchmarks AlphaFold3 (AF3)/“co-folding” methods with 2 new stringent performance tests.
Thread below - but first some links:
A longer take:
fraserlab.com/2025/12/29/k...
Preprint:
www.biorxiv.org/content/10.6...
Thread below - but first some links:
A longer take:
fraserlab.com/2025/12/29/k...
Preprint:
www.biorxiv.org/content/10.6...
Reposted by James Fraser
Large scale prospective evaluation of co-folding across 557 Mac1-ligand complexes and three virtual screens https://www.biorxiv.org/content/10.64898/2025.12.25.696505v1
December 29, 2025 at 1:46 AM
Large scale prospective evaluation of co-folding across 557 Mac1-ligand complexes and three virtual screens https://www.biorxiv.org/content/10.64898/2025.12.25.696505v1
Reposted by James Fraser
Large scale prospective evaluation of co-folding across 557 Mac1-ligand complexes and three virtual screens [new]
Mac1 co-folding eval: Pose prediction, conform. change, & hit ID post-training.
Mac1 co-folding eval: Pose prediction, conform. change, & hit ID post-training.
December 29, 2025 at 2:38 AM
Large scale prospective evaluation of co-folding across 557 Mac1-ligand complexes and three virtual screens [new]
Mac1 co-folding eval: Pose prediction, conform. change, & hit ID post-training.
Mac1 co-folding eval: Pose prediction, conform. change, & hit ID post-training.
Reposted by James Fraser
Online today, the journal version of our ( @nanigrotjahn.bsky.social @attychang.bsky.social @mmedina300kv.bsky.social) manuscript from earlier this year describing membrane thickness measurement in cells with #teamtomo! rupress.org/jcb/article/...
Surface Morphometrics reveals local membrane thickness variation in organellar subcompartments | Journal of Cell Biology | Rockefeller University Press
Medina, Chang et al. introduce a new method based on the Surface Morphometrics pipeline to measure global and local thicknesses of organellar membranes fro
rupress.org
December 26, 2025 at 8:21 PM
Online today, the journal version of our ( @nanigrotjahn.bsky.social @attychang.bsky.social @mmedina300kv.bsky.social) manuscript from earlier this year describing membrane thickness measurement in cells with #teamtomo! rupress.org/jcb/article/...
Reposted by James Fraser
Last TTPD of the year! We talk about trends over 2025 and predictions for 2026 and beyond! @fraserlab.com
podcasts.apple.com/us/podcast/s...
podcasts.apple.com/us/podcast/s...
Science Tree Farm
Podcast Episode · The Tortured Proteins Department · 12/20/2025 · 1h 7m
podcasts.apple.com
December 20, 2025 at 11:03 PM
Last TTPD of the year! We talk about trends over 2025 and predictions for 2026 and beyond! @fraserlab.com
podcasts.apple.com/us/podcast/s...
podcasts.apple.com/us/podcast/s...
Reposted by James Fraser
New preprint! Entropy drives molecular recognition, yet most structure-based drug design ignores it because it is difficult to measure. X-ray crystallography captures ensembles, not single structures. Can we extract thermodynamically meaningful entropy from them?
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Crystallographic Ensembles Reveal the Structural Basis of Binding Entropy in SARS-CoV2 Macrodomain
Structure-based drug design has traditionally focused on optimizing static, enthalpic interactions between ligands and proteins or on displacing binding site solvent molecules to entropically favor bi...
www.biorxiv.org
December 1, 2025 at 2:28 PM
New preprint! Entropy drives molecular recognition, yet most structure-based drug design ignores it because it is difficult to measure. X-ray crystallography captures ensembles, not single structures. Can we extract thermodynamically meaningful entropy from them?
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by James Fraser
Crystallographic Ensembles Reveal the Structural Basis of Binding Entropy in SARS-CoV2 Macrodomain https://www.biorxiv.org/content/10.1101/2025.11.25.690589v1
November 27, 2025 at 2:47 AM
Crystallographic Ensembles Reveal the Structural Basis of Binding Entropy in SARS-CoV2 Macrodomain https://www.biorxiv.org/content/10.1101/2025.11.25.690589v1
Reposted by James Fraser
TTPD Episode 9 with @fraserlab.com: I Can Do It With a Broken Grant Cycle
(Sorry for the crappy audio in places!)
Topics: Government Shutdown/Reopening, Travels, Jane Richardson's impact (en.wikipedia.org/wiki/Jane_S....), Arena BioWorks closing, AI review tools
wankowiczlab.com/2025/11/24/T...
(Sorry for the crappy audio in places!)
Topics: Government Shutdown/Reopening, Travels, Jane Richardson's impact (en.wikipedia.org/wiki/Jane_S....), Arena BioWorks closing, AI review tools
wankowiczlab.com/2025/11/24/T...
November 24, 2025 at 3:22 PM
TTPD Episode 9 with @fraserlab.com: I Can Do It With a Broken Grant Cycle
(Sorry for the crappy audio in places!)
Topics: Government Shutdown/Reopening, Travels, Jane Richardson's impact (en.wikipedia.org/wiki/Jane_S....), Arena BioWorks closing, AI review tools
wankowiczlab.com/2025/11/24/T...
(Sorry for the crappy audio in places!)
Topics: Government Shutdown/Reopening, Travels, Jane Richardson's impact (en.wikipedia.org/wiki/Jane_S....), Arena BioWorks closing, AI review tools
wankowiczlab.com/2025/11/24/T...
Reposted by James Fraser
Can’t wait to be there repping @arpa-h.bsky.social and spreading the word about amazing work happening with @fraserlab.com, @qbi-ucsf.bsky.social, and others!
We look forward to welcoming Dr. @andykilianski.bsky.social, Program Manager at ARPA-H for a seminar hosted by James Fraser.
Learn about how ARPA-H is investing in bold, transformative research to shape the future of health in the United States: qbi.ucsf.edu/seminar-kili...
Learn about how ARPA-H is investing in bold, transformative research to shape the future of health in the United States: qbi.ucsf.edu/seminar-kili...
October 27, 2025 at 2:39 AM
Can’t wait to be there repping @arpa-h.bsky.social and spreading the word about amazing work happening with @fraserlab.com, @qbi-ucsf.bsky.social, and others!
Reposted by James Fraser
TTPD #8 with @fraserlab.com: Open access, Clear science, Full hearts, Can’t lose!
We chat about the Compact for Academic Excellence in Higher Education, HHMI open access, the government shutdown, the BEAR, the Nobel Prizes, and The Life of a Showgirl! wankowiczlab.com/2025/10/23/T...
We chat about the Compact for Academic Excellence in Higher Education, HHMI open access, the government shutdown, the BEAR, the Nobel Prizes, and The Life of a Showgirl! wankowiczlab.com/2025/10/23/T...
The Tortured Proteins Department, Episode 8
This is the official web page for the Stephanie Wankowicz Lab at Vanderbilt University.
wankowiczlab.com
October 23, 2025 at 3:39 PM
TTPD #8 with @fraserlab.com: Open access, Clear science, Full hearts, Can’t lose!
We chat about the Compact for Academic Excellence in Higher Education, HHMI open access, the government shutdown, the BEAR, the Nobel Prizes, and The Life of a Showgirl! wankowiczlab.com/2025/10/23/T...
We chat about the Compact for Academic Excellence in Higher Education, HHMI open access, the government shutdown, the BEAR, the Nobel Prizes, and The Life of a Showgirl! wankowiczlab.com/2025/10/23/T...
Reposted by James Fraser
Two main ways to encode structural heterogeneity beyond B-factors or TLS: multiconformer or multi-model (ensemble) models.
October 21, 2025 at 4:30 PM
Two main ways to encode structural heterogeneity beyond B-factors or TLS: multiconformer or multi-model (ensemble) models.
Reposted by James Fraser
I spend a lot of time talking to potential grantees about our open science policy. Some field notes here:
open.substack.com/pub/seemay/p...
open.substack.com/pub/seemay/p...
Why careerism can be bad for science training
Some field notes from scholarly publishing discussions with scientists
open.substack.com
October 21, 2025 at 3:52 PM
I spend a lot of time talking to potential grantees about our open science policy. Some field notes here:
open.substack.com/pub/seemay/p...
open.substack.com/pub/seemay/p...
Reposted by James Fraser
The Diffuse Project is looking for an amazing Project Manager to help us achieve our goal of unlocking protein dynamics! Are you a scientist who naturally loves organization, coordination, problem solving and working with a diverse team of scientists & engineers?
October 7, 2025 at 2:11 AM
The Diffuse Project is looking for an amazing Project Manager to help us achieve our goal of unlocking protein dynamics! Are you a scientist who naturally loves organization, coordination, problem solving and working with a diverse team of scientists & engineers?