Prism Science
@prismscienceorg.bsky.social
Prism is building the full stack of technologies and algorithms necessary to make protein motion measurable, actionable, and predictable. Learn more at prismscience.org
Proteins are always moving. They wiggle. They jiggle. They interact with their surroundings. That movement drives their function. Yet the motion stays mostly invisible. We cannot understand protein function, engineer it, or correct it until we can see the motion and predict it. prismscience.org
Prism | Revealing the Dynamics of Life
Dynamic structural data, models, and language to become standard across the field. At scale, this is how we predict conformational ensembles across all of biology.
prismscience.org
We have not yet tapped the full potential of cryoEM. The method revolutionized structural bio with atomic-level detail, but has largely focused on proteins’ common lowest-energy states. With enough samples, cryoEM sees a broader energy landscape: It can capture *rare* states.
We need new ways to understand disease & design drugs. Protein motion holds the answer.
Diffuse scattering is hard to compare quantitatively across experiments, let alone across synchrotrons. A new DiffUSE Project update shows diffuse maps reproducing across CHESS and ALS. Read the project update: diffuse.science/posts/reprod...
Coffee is for Closers: making Mac1 diffuse scattering reproducible
diffuse scattering reproducible, yay!
diffuse.science
Diffuse scattering can encode correlated protein motions, but standard pipelines often discard it as background. mdx2 is an open-source Python toolkit for carrying that signal through processing. Read @meisborg.bsky.social's overview and try mdx2: diffuse.science/posts/mdx2/
Revealing hidden signals in raw X-ray crystallography data with mdx2
Mdx2 is a powerful and open-source toolkit for diffuse data processing.
diffuse.science
Same mission, but an expanded vision for revolutionizing structural biology to better capture protein motion. Launching September 8.
WaterFlow: Prediction of Ordered Water Molecule Positions on Protein Structures https://www.biorxiv.org/content/10.64898/2026.08.26.747373v1
Check out our latest! 🌊
Stephanie Wankowicz@stephanieaw.bsky.social · 2w agoNew pub from @diffuseproject.bsky.social! Ordered water molecules mediate protein stability, ligand binding, and catalysis. Predicting them lags far behind protein structure prediction. We developed WaterFlow, a new state-of-the-art method for ordered water placement. www.biorxiv.org/content/10.6...
DiffUSE is rebuilding GOODVIBES, a forward model for lattice vibrations in diffuse scattering, in fully open-source Python that handles any space group or unit cell. Stephen Thornton posts the progress and open questions. diffuse.science/posts/goodvi... #openscience
Most structures in the PDB report one set of coordinates. The experimental data behind them, in both X-ray crystallography and cryo-EM, is produced by an ensemble. New work recovers that hidden signal at scale in over 60,000 structures. thestacks.org/publications...
Recovering Conformational Heterogeneity from the Protein Data Bank at Scale
An Ensemble Dataset of over 60,000 Structures
thestacks.org
New in BANDICOOT: color each altloc a distinct hue, so you see heterogeneity while you build. Each added alternate conformation is auto hue-shifted from the last; remove them all and the residue returns to bulk color. Configurable and open source! diffuse.science/post/bandico... #compbio
Displaying Conformational Heterogeneity in BANDICOOT
In preparation for hierarchical hetereogeneity encoding, BANDICOOT has a new, more intuitive display mode for alternate conformations.
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 · 5mo 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