The DiffUSE Project
@diffuseproject.bsky.social
Infrastructure for learning and representing protein motions from structural data Learn more at https://diffuse.science
An mmCIF file can say a residue has two alternate conformations and how often each appears. It cannot say which alternates occur together in the same copy. A draft proposal for recording that correlation, plus a tool to inspect it: diffuse.science/posts/mmcif-...
mmCIF Explorer and the Heterogeneity Proposal
A playground for the PDBx/mmCIF file exploration, a look at the current proposal for encoding correlated heterogeneity
diffuse.science
In our latest blog, @fraserlab.com graduate student Taylor Womack discusses his roadmap before the results: how he plans to separate lattice vibrations from internal protein motion, which open tools he is using, and which parts are still unresolved. Feedback welcome. diffuse.science/posts/taylor...
Is it all just the lattice?
Towards a complete forward model of diffuse scattering
xtraj.py
New TTPD episode discusses two bioRxiv preprints, revisits the Bethesda Declaration one year on, and public pushback to the OMB funding rule. Plus: where blogs end and peer review begins. diffuse.science/posts/TTPD-16/ #StructuralBiology #Biophysics #OpenScience
Bandicoot reengineers Coot 0.9 for macOS Tahoe: toolbars rebuilt, UI moved from Python 2 to C++, atom picking and labels reworked. Now with built-in pandda.inspect for examining partial-occupancy and alt conformations. diffuse.science/post/bandico...
BANDICOOT: Coot 0.9 That Runs on MacOS Tahoe
Reviving Coot 0.9 for MacOS Tahoe as Bandicoot, a bespoke and integrated molecular modeling environment.
diffuse.science
Why do protein-function AI models look great on benchmarks but disappoint in practice? Often "leakage": proteins meant for testing slip into training data over time, inflating scores. PLUG is a tool to build cleaner training sets. Read Clay's work: diffuse.science/post/plug-be... #proteinML
Introducing PLUG: A Compiler for Leakage-free Protein Function Benchmarking
Leakage-free Training to Predict Protein Function
diffuse.science
Unlocking protein dynamics requires infrastructure we all can access. ICYMI: all of our software packages live on GitHub, updated in the open: github.com/diff-use
diffUSE
diffUSE has 15 repositories available. Follow their code on GitHub.
github.com
Open science is useful science. One effort we are developing are logbooks where we share research as it happens: what works, what doesn't, what we've learned. Led by DiffUSE Scientist Steve Meisburger (@meisborg.bsky.social). See the latest: diffuse.science/logbook/beam... #OpenScience
What's happening in protein dynamics research right now? Jaime & Stephanie break down NIH policy changes, preprints & the conformational ensembles conference. New episode up: diffuse.science/posts/TTPD-15/ #StructuralBiology
Bulk solvent fills ~half a protein crystal. Modeling this is required for a good fit to experimental data. How best to model this remains an open question. New from diffUSE: a Phenix patch to supply your own solvent map (MD, 3D-RISM, EDEN, neural nets). Read more here: thestacks.org/publications...
thestacks.org
We share science at The DiffUSE Project in a few ways: blogs to contextualize motivation and intuition, scholarly outputs for methods, data, code, and a citable DOI. All open and shared rapidly for the best science. Our latest: doi.org/10.82153/jkx...
sampleworks: A Modular Platform for Experimentally Guided Biomolecular Ensemble Generation
Structural biology increasingly relies on machine learning-based structure predictors, enabling accurate atomic-level structure prediction at scale. However, predicting conformational ensembles…
doi.org
We present sampleworks, an open, modular platform for generating and evaluating biomolecular conformational ensembles from structure predictors guided by experimental data doi.org/10.82153/jkx....
Want to shape the future of structural biology? We are seeking a Project Manager to help lead the DiffUSE Project, guiding ML researchers, computational scientists, national labs, and university partners. Apply: buff.ly/gZlj9AP #StructuralBiology #MachineLearning #Hiring #AcademicSky
Project Manager - DiffUSE Project
ABOUT DIFFUSE The DiffUSE Project is building open infrastructure to study protein dynamics using experimental data. The project spans wet-lab collaborators, computational scientists, ML researchers,…
jobs.ashbyhq.com
Simulations can be valuable but there is a huge need for scalable experiments that probe protein dynamics- of course we're expanding our work here and there's also great work from others @hkws.bsky.social @ginaelnesr.bsky.social Basile Wicky (not on bsky) @diffuseproject.bsky.social
The DiffUSE Project wants examples where structural heterogeneity matters but cannot be encoded in PDBx/mmCIF. X-ray, cryo-EM, time-resolved, multi-map, or fragment screening data welcome. Submit yours: diffuse.science/submit/
Submit Examples of Heterogeneous Structural Data
The DiffUSE Project
diffuse.science
ICYMI: The latest Tortured Proteins Department episode. @stephanieaw.bsky.social and @fraserlab.com on: NIH strategic plan comments (due 5/26), AI lab guidelines, two new cryo-EM preprints, training scientists for what's next diffuse.science/posts/TTPD-14/
Speakers include: @nozomi-ando.bsky.social @hkws.bsky.social, @pilarcossio.bsky.social, @cjjackson.bsky.social, @karsonchrispens.bsky.social, @alisiafadini.bsky.social, @thompson-lab.bsky.social, Joey Davis, Alex Bronstein, Rohith Krishna, Matthew McPartlon, Frederic Poitevin
Hosted in partnership with the DiffUSE Project! 🎉👇
Stephanie Wankowicz@stephanieaw.bsky.social · 4mo agoYear 3 of Conformational Ensembles Conference! The most compelling questions in structural biology cannot be effectively addressed with a single structure. We have a stellar lineup of people looking at and answering these questions. @fraserlab.com More information: conformationalensembles.github.io
Congrats to DiffUSE lead Stephanie Wankowicz @stephanieaw.bsky.social, on winning the inaugural Sheldrick Award! Her work on entropic flexibility and reproducibility in structural biology is core to what we're building. #crystallography #structuralbiology #openscience aucryst.org/sheldrick-aw...
We observed a tradeoff: weak guidance improves fit to data without wrecking protein geometry. But strong guidance destroys the geometry. Interestingly, models differ a lot in how they handle this despite similar architectures.
Excited to share Sampleworks led by @karsonchrispens.bsky.social with @diffuseproject.bsky.social. It's a modular framework connecting structure predictors to experimental data and guidance methods. Swap predictors or guidance methods. All open and made to be built upon. t.co/fvNHH3gfVu
https://diffuse.science/posts/sampleworks/
t.co
Radial is live! A new organization at @asterainstitute.bsky.social bringing together structural biologists, engineers, and ML scientists to redesign how we do science. @statnews.com has the story: www.statnews.com/2026/03/11/r...
New nonprofit launches with at least $500 million to modernize scientific process for AI era
A new nonprofit called Radial is launching with at least $500 million to modernize the scientific process for the AI era.
statnews.com
MD simulations show that diffuse scattering patterns shift depending on whether ligand or a buffer molecule occupies the binding pocket. The differences are quantitatively significant, a promising sign that experiments could detect these changes. Read more: diffuse.science/post/shake-i...
Shake It Up!
MD simulations of changes in diffuse scattering depending on ligand binding
diffuse.science
Tomorrow (2/27) 3 pm ET, DiffUSE Project Scientist Steve Meisburger presents "Diffuse Scattering Wars (Episode IV): A New Hope for Structural Biology" Learn how diffuse scattering could reveal what AI structure predictors are missing. Join here: www.chess.cornell.edu/science/ches...
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?
Happy @diffuseproject.bsky.social launch day! Check out our latest effort. We're grappling with how to better understand protein dynamics and capture/share the information that would best allow the community to make use of that data. Take a look!
Seemay Chou@seemaychou.bsky.social · 12mo agoWhat’s the next PDB? Maybe it’s …the PDB. We just launched @diffuseproject.bsky.social a structural biology initiative exploring protein motion & rethinking how we generate and use experimental data. Quick 🧵👇 www.diffuse.science
What’s the next PDB? Maybe it’s …the PDB. We just launched @diffuseproject.bsky.social a structural biology initiative exploring protein motion & rethinking how we generate and use experimental data. Quick 🧵👇 www.diffuse.science
The Diffuse Project
The Diffuse Project
diffuse.science
Announcing the Diffuse Project! We're unlocking protein dynamics through diffuse X-ray scattering - the overlooked signal that could revolutionize how we understand protein motion. seemay.substack.com/p/from-syste...
From systems operators to systems architects
Going up a level from data generation to think about the data systems we design and embed
seemay.substack.com