Gabriel Rocklin

Gabriel Rocklin

@grocklin.bsky.social

Digests proteins. High-throughput protein biophysics and design, Northwestern University. www.rocklinlab.org

1.4K followers389 following164 posts

Gabriel Rocklin reposted

Replying to @pedrobeltrao.bsky.social

We've actually been working on this very actively and have quite promising results on larger/higher stability proteins using an improved method. Looking for funding to buy some (a lot of) oligos... any pointers? It's within reach...

Thread coming later but I think people will like this!! 2 million stability measurements plus a predictive model for deltaG (not ddG)

bioRxiv Biophysics@biorxiv-biophys.bsky.social

Accurate protein stability prediction for small domains using mega-scale experiments https://www.biorxiv.org/content/10.64898/2026.05.19.726285v1

Happy to share this in its published form! More than any project I've worked on, this was a huge team effort, so thank you so much to that team! Especially @ajrferrari.bsky.social www.nature.com/articles/s41...

nature.comLarge-scale discovery, analysis and design of protein energy landscapes - NatureAn analysis of 5,778 domains 28–64 amino acids in length reveals hidden variation in conformational fluctuations, even between sequences sharing the same fold and global folding stability.
Gabriel Rocklin@grocklin.bsky.social

Small proteins can be more complex than they look! We know proteins fluctuate between different conformations- but by how much? How does it vary from protein to protein? Can highly stable domains have low stability segments? @ajrferrari.bsky.social experimentally tested >5,000 domains to find out!

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Happy to share this in its published form! More than any project I've worked on, this was a huge team effort, so thank you so much to that team! Especially @ajrferrari.bsky.social www.nature.com/articles/s41...

nature.comLarge-scale discovery, analysis and design of protein energy landscapes - NatureAn analysis of 5,778 domains 28–64 amino acids in length reveals hidden variation in conformational fluctuations, even between sequences sharing the same fold and global folding stability.
Gabriel Rocklin@grocklin.bsky.social

Small proteins can be more complex than they look! We know proteins fluctuate between different conformations- but by how much? How does it vary from protein to protein? Can highly stable domains have low stability segments? @ajrferrari.bsky.social experimentally tested >5,000 domains to find out!

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It's horrifying to see how the admin and DOGE have intentionally decimated the NIH through layoffs, freezes, and multi-year funding (a stealth budget cut)- so that NIH grad students have to moonlight as admins to get grants out bsky.app/profile/maxk...

Max Kozlov@maxkozlov.bsky.social

The staffing crunch is so severe that the NIMH has asked its intramural grad students and postdocs to volunteer in this admin capacity temporarily. Also: the institute's acting deputy director - the second in charge - is devoting half of her time to grants management.

Happy to share this in its published form! More than any project I've worked on, this was a huge team effort, so thank you so much to that team! Especially @ajrferrari.bsky.social www.nature.com/articles/s41...

nature.comLarge-scale discovery, analysis and design of protein energy landscapes - NatureAn analysis of 5,778 domains 28–64 amino acids in length reveals hidden variation in conformational fluctuations, even between sequences sharing the same fold and global folding stability.
Gabriel Rocklin@grocklin.bsky.social

Small proteins can be more complex than they look! We know proteins fluctuate between different conformations- but by how much? How does it vary from protein to protein? Can highly stable domains have low stability segments? @ajrferrari.bsky.social experimentally tested >5,000 domains to find out!

View full thread

Happy to share this in its published form! More than any project I've worked on, this was a huge team effort, so thank you so much to that team! Especially @ajrferrari.bsky.social www.nature.com/articles/s41...

nature.comLarge-scale discovery, analysis and design of protein energy landscapes - NatureAn analysis of 5,778 domains 28–64 amino acids in length reveals hidden variation in conformational fluctuations, even between sequences sharing the same fold and global folding stability.
Gabriel Rocklin@grocklin.bsky.social

Small proteins can be more complex than they look! We know proteins fluctuate between different conformations- but by how much? How does it vary from protein to protein? Can highly stable domains have low stability segments? @ajrferrari.bsky.social experimentally tested >5,000 domains to find out!

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Relying exclusively on MD simulations to build dynamics into ML models runs some risk of garbage in/garbage out- simulations are not "gold standards" (our experiments in D2O aren't perfect gold standards either for that matter!). Excited to benchmark/improve sims with exp data!!

Happy to share this in its published form! More than any project I've worked on, this was a huge team effort, so thank you so much to that team! Especially @ajrferrari.bsky.social www.nature.com/articles/s41...

nature.comLarge-scale discovery, analysis and design of protein energy landscapes - NatureAn analysis of 5,778 domains 28–64 amino acids in length reveals hidden variation in conformational fluctuations, even between sequences sharing the same fold and global folding stability.
Gabriel Rocklin@grocklin.bsky.social

Small proteins can be more complex than they look! We know proteins fluctuate between different conformations- but by how much? How does it vary from protein to protein? Can highly stable domains have low stability segments? @ajrferrari.bsky.social experimentally tested >5,000 domains to find out!

I also want to especially thank Mike Guttman at UW for sitting with me for hours/days to train me in HDX-MS even though I was a postdoc in a different lab with a weird idea and he was just starting a faculty position. It was super generous

It's amazing to see explosive growth in machine learning/modeling of protein structures, but we have so far to go to accurately model/incorporate dynamics and fluctuations. Especially because these happen at many scales- from rotamer shifts to global unfolding and all in between

Gabriel Rocklin reposted

If you missed the preprint, now is a good time to read the journal version of @grocklin.bsky.social et al’s fantastic paper on multiplexed HDX measurements Large-scale discovery, analysis and design of protein energy landscapes doi.org/10.1038/s415...

bioRxiv Biophysics@biorxiv-biophys.bsky.social

Large-scale discovery, analysis, and design of protein energy landscapes https://www.biorxiv.org/content/10.1101/2025.03.20.644235v1

Gabriel Rocklin reposted

New lab preprint: if ML struggles with extrapolation, let's expand the diversity of training data with gene synth, DNA shuffling, and ML gen.... also lots of #FluorescentProteins #ProteinEngineering #MachineLearning #SyntheticBiology 1/n

bioRxiv Synthetic Biology@biorxiv-synthbio.bsky.social

High Diversity Gene Libraries Facilitate Machine Learning Guided Exploration of Fluorescent Protein Sequence Space https://www.biorxiv.org/content/10.64898/2026.03.01.706892v1

Gabriel Rocklin reposted

I’m looking to hire a research technician for my lab at Harvard & DFCI, who would primarily work in the wet lab expressing and characterizing designed proteins, starting this summer. A great role for a recent college grad looking for an immersive research experience before grad school.

Gabriel Rocklin reposted

The most precious commodity you have is your attention. You don’t have to waste it on poor-faith debates or arguments with strangers if you don’t think they’ll be productive. You can prioritize the things that matter to you and make your life richer.

Gabriel Rocklin reposted

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I hope this is useful and we're excited to use this approach to explore more protein stresses- shelf life, vortexing, freeze-thaw, etc. I also love this paper because it's our lab's first time using quantitative proteomics! Congrats Cydney et al!!

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There’s much more in the paper, including the surprising observation that higher folding stability correlates with aggregation even controlling for hydrophobicity (?!) Stabilities measured by Kotaro Tsuboyama!

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We expressed the protein domains together as a mixture in one E. coli culture, purified our mixture of domains and concentrated to 10mg/mL, then used TMT proteomics to monitor the change in soluble protein abundance after high temp/low pH.

Gabriel Rocklin reposted

quick reminder to come see @grocklin.bsky.social tonight at @mit.edu!

Join us in Room 181, Building 68 @mit.edu on October 22nd 2025 @ 7pm EDT to see @grocklin.bsky.social present a mind blowing amount of data and learn what becomes possible at this scale "Predicting protein folding stability and aggregation propensity using large-scale experiments" bpdmc.org

Gabriel Rocklin reposted

Join us in Room 181, Building 68 @mit.edu on October 22nd 2025 @ 7pm EDT to see @grocklin.bsky.social present a mind blowing amount of data and learn what becomes possible at this scale "Predicting protein folding stability and aggregation propensity using large-scale experiments" bpdmc.org

bpdmc.orgscheduleintroduction and membership Boston Protein Design and Modeling Club (BPDMC) is a community of computational protein engineers and modelers from both academia and industry. While we are based in Boston...

Gabriel Rocklin reposted

Announcing such a major change to NSF GRFP this late in the cycle is incredibly cruel. 2nd yr students (mine included) have been working so hard on their proposals despite ongoing uncertainty. They are driven and passionate about being outstanding scientists and helping those coming up behind them.

Gabriel Rocklin reposted

Cecilia Payne-Gaposchkin ✨ figured out what stars are made of ✨ when she was just 25. 🔭🧪 Her PhD thesis basically established the Harvard astro department — at a time when Harvard didn't officially allow woman students. I wrote this little profile to mark the 100th anniversary of her thesis:

sciencenews.orgHow a Harvard maverick forever changed our concept of the starsAt just 25, Cecilia Payne-Gaposchkin applied quantum physics to a treasure trove of astronomical observations to show that stars are mostly hydrogen and helium.
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Gabriel Rocklin reposted

Vought and his “no more NIH money out the door” footnote is a power struggle. Between R’s getting antsy about hard votes and Senate signaling support for science funding, Vought had to signal his dominance in some way. Now is the real test: are R’s more afraid of Trump et al. or their constituents?

Gabriel Rocklin reposted

The NIH can’t award ANY grants to outside researchers under new WH restriction, reports @wsj.com. The pause came in the form of a footnote from OMB Director Vought, in a document that doles out federal funds to the NIH. Prelude to rescissions, especially after his comments over the weekend?

wsj.comTrump Administration Puts New Chokehold on Billions in Health-Research FundingThe National Institutes of Health can’t award grants to outside researchers under a new White House restriction.

Gabriel Rocklin reposted

#MorganLabatND is hiring a research technician!! We are looking for an aspiring biochemistry researcher that shares our community values, is curious about the world around them, and brings a unique perspective to our team. (1/2) jobs.smartrecruiters.com/UniversityOf...

jobs.smartrecruiters.comResearch TechnicianCompany Description: The University of Notre Dame is more than a workplace; it is a vibrant, mission-driven community where every employee is valued and supported. Rooted in a tradition of excellence ...