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Hannah Wayment-Steele @hkws.bsky.social · 23d

Cricket and Willow hosted a W-S lab dinner!

Hannah Wayment-Steele @hkws.bsky.social · May 23

The W-S lab is seeking to hire a research scientist!

This person will lead wet-lab innovations in our team as we combine AI and experiments to understand and design dynamics!

Thanks for sharing/RTs!

jobs.wisc.edu/jobs/scienti...

Scientist and Lab Operations Coordinator - Madison, Wisconsin, United States

Job Summary: The Wayment-Steele Lab seeks a Research Scientist to lead experimental operations within our highly interdisciplinary team, integrating both computational "dry" and experimental "wet" l...

jobs.wisc.edu

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Reposted by Hannah Wayment-Steele

James Fraser @fraserlab.com · May 20

We are looking to hire (yes, even in this economy!) a jr. specialist to train in protein prep/structural biology related to our AVOID-ome work as part of openadmet.org.

A great position for someone who is looking to be a tech for a few years before grad or med school.

aprecruit.ucsf.edu/JPF05424

Junior/Assistant/Associate/Full Specialist Positions Available

University of California, San Francisco is hiring. Apply now!

aprecruit.ucsf.edu

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Reposted by Hannah Wayment-Steele

Stephanie Wankowicz @stephanieaw.bsky.social · Mar 31

Join us for the 2nd Macromolecular Conformational Ensembles Conference on June 9th/10th at UCSF. The most compelling questions in structural biology cannot be effectively addressed using only a single structure. conformationalensembles.github.io @fraserlab.bsky.social

Conformational Ensemble

conformationalensembles.github.io

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Reposted by Hannah Wayment-Steele

Gina El Nesr @ginaelnesr.bsky.social · May 12

someone said we need a meme

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Hannah Wayment-Steele @hkws.bsky.social · May 9

btw in the name of getting NMR dynamics data out there, RelaxDB is available at the Dyna-1 huggingface! Go check it out huggingface.co/gelnesr/Dyna-1

gelnesr/Dyna-1 · Hugging Face

We’re on a journey to advance and democratize artificial intelligence through open source and open science.

huggingface.co

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Hannah Wayment-Steele @hkws.bsky.social · May 9

Did some quick curation for ~30 of 133 proteins in our new dataset RelaxDB, which is the first of its kind to gather experimental info on timescales of motions per residue. The x-axis is intentionally silly to make a point - these dynamics expts do not use more than 10% D2O in samples.

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Hannah Wayment-Steele @hkws.bsky.social · May 9

@dereklowe.bsky.social The paper you cite discusses difference when entire solvent is D2O. It could be that D2O partitions away from protein when it’s there at 5% since the paper’s main point is H2O has increased interactions with proteins. Curious if anyone’s investigated that!

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Hannah Wayment-Steele @hkws.bsky.social · May 9

this is why many protein nmr spectroscopists only use 5-10% D2O! I hope this doesn’t deter people from what imo is a super undervalued source of data

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Hannah Wayment-Steele @hkws.bsky.social · May 5

👏 models in nmr structure != thermodynamics 👏
Structures I’ve been part of include the top-X most probable structures. Same as how the top-X-scoring models from a Rosetta run wouldn’t be a thermodynamic ensemble.

Kresten Lindorff-Larsen @lindorfflarsen.bsky.social · May 4

While this paper looks interesting, let me just say (again) that (essentially all) NMR ensembles in the PDB are NOT thermodynamic ensembles or meant to represent these. They are "uncertainty ensembles" and using them to benchmark machine learning (or other) models of dynamics is not a good idea.

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Hannah Wayment-Steele @hkws.bsky.social · Apr 28

If we wanna make accurate boltzmann samplers, we gotta know what distributions they should be sampling 😁 These change in the presence/absence of ligands, and there are multiple systems for which this is well-understood by this point experimentally.

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Hannah Wayment-Steele @hkws.bsky.social · Apr 28

BioEmu actually doesn't pass this test for AdK: majority of samples are in closed state (1AKE), which is the same intrinsic bias that AF2 + random sampling gets.

I don't know the other apo/holo systems bioEmu looks at as well, but same story: sampled density is primarily at the holo state.

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Hannah Wayment-Steele @hkws.bsky.social · Apr 28

You can see this in this FRET data for AdK here: in ligand-free form, the open state is more populated than closed.

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Hannah Wayment-Steele @hkws.bsky.social · Apr 28

Really nice resource from @delalamo.xyz !!

Wanna mention the "AdK test" we're noticing newer DL methods fall short on:

many proteins (like AdK) that have apo/holo conf change sample both the apo/holo state even without ligand bound. But w/o ligand bound, they *are mainly in the apo state*

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Reposted by Hannah Wayment-Steele

ML for Protein Engineering Seminar @ml4proteins.bsky.social · Apr 22

Next Tues (4/29) at **4:30PM** ET, we will have @ginaelnesr.bsky.social @hkws.bsky.social present "Learning millisecond protein dynamics from what is missing in NMR spectra"

Paper: biorxiv.org/content/10.1...

Sign up on our website for zoom links!

Learning millisecond protein dynamics from what is missing in NMR spectra

Many proteins’ biological functions rely on interconversions between multiple conformations occurring at micro-to millisecond (µs-ms) timescales. A lack of standardized, large-scale experimental data ...

biorxiv.org

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Reposted by Hannah Wayment-Steele

Rita Strack @ritastrack.bsky.social · Apr 10

Your yearly reminder to acknowledge the core facilities you use and their staff scientists in your papers. These scientists are a crucial part of the scientific ecosystem and to continue to exist they need tangible credit for their work. Plus their associated expertise adds credibility to your work.

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Hannah Wayment-Steele @hkws.bsky.social · Mar 21

I am sure future improvements exist over what we did! We removed deuterated samples (incomplete back-exchange) and entries with more than 12 15N assignments missing in a row. This is why we call this a "bold assumption", to me the proof is in the pudding, that we got a model with signal at all!

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Hannah Wayment-Steele @hkws.bsky.social · Mar 21

Hi Gabe! Yeah we thought of af pair (no MSA) as upper limit but what you’re proposing would also be control for pair rep.
To me, the kicker things we want to predict are coordinated motions that have low prob. Saw hints of that with CypA. I don’t think people would think of that as flexibility …

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Reposted by Hannah Wayment-Steele

Kevin K. Yang 楊凱筌 @kevinkaichuang.bsky.social · Mar 20

Unassigned nitrogens in nmr data often indicate biologically relevant motion in proteins, and this can be used train deep learning models of protein dynamics!

Hannah Wayment-Steele
@ginaelnesr.bsky.social @sokrypton.org

www.biorxiv.org/content/10.1...

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Reposted by Hannah Wayment-Steele

Gina El Nesr @ginaelnesr.bsky.social · Mar 20

Protein function often depends on protein dynamics. To design proteins that function like natural ones, how do we predict their dynamics?

@hkws.bsky.social and I are thrilled to share the first big, experimental datasets on protein dynamics and our new model: Dyna-1!

🧵

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Hannah Wayment-Steele @hkws.bsky.social · Mar 20

Thank you so much to the amazing Doro Kern for dreaming big w me. Thank you to @ramith.fyi, Hasindu, and @sokrypton.org for pushing these ideas in early days! last but not least, thanks to @jcchildsfund.bsky.social and @hhmi.org for funding :))

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Hannah Wayment-Steele @hkws.bsky.social · Mar 20

Tremendous thank you to partner-in-crime @ginaelnesr.bsky.social. This collaboration started when she offered to clean a metadata spreadsheet, and she ended up pushing the deep learning we tested so much further than I could have alone!

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Hannah Wayment-Steele @hkws.bsky.social · Mar 20

Moral of the story: useful data is out there at many degrees of quality, but we need to know how to interpret the data. We're so excited to see where these models and data go next!
Paper: rb.gy/de5axp
Dyna-1 colab (thanks to @ginaelnesr.bsky.social ) and RelaxDB: github.com/WaymentSteel...

GitHub - WaymentSteeleLab/Dyna-1: Model for predicting micro-millisecond motions from protein sequence and/or structure

Model for predicting micro-millisecond motions from protein sequence and/or structure - WaymentSteeleLab/Dyna-1

github.com

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Hannah Wayment-Steele @hkws.bsky.social · Mar 20

Dyna-1 has predictive power in the big dogs of dynamics experiments: CPMG relaxation-dispersion. Dyna-1 predicted high p(exchange) in some aa's that typical data treatment says has no Rex, but more careful consideration says is real (NMR aficionados: unsuppressed R2).

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Hannah Wayment-Steele @hkws.bsky.social · Mar 20

There are so many interesting things that Dyna-1 predicts, but I wanna talk about a trend it didn't predict in RelaxDB! We realized that in many RelaxDB datasets where Dyna-1 did poorly, the Rex came from phosphate buffer binding/unbinding to the protein, an experimental artefact.

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