Fried Lab JHU

Wrapping up an amazing 4th annual Mass Spec Day @jhu.edu is @jyates.bsky.social with a talk on the mechanism of CF. “Every day is mass spec day!” Thank you to our speakers, sponsors, and my fellow co-organizers. Looking forward to seeing yall @asms.org in #Baltimore!

Wouldn’t have been possible without the indefatigable @leunglab.bsky.social a brilliant co-organizer! Very pleased the day was such a success. Special
Thanks to student speakers who really took things up a notch!

Though putting on FCBIS 2025 was a lot of work, I think it was worth it and hearing this from friends is so satisfying! I’m glad we could bring our community together for a day of exchange, learning, and good times! Next year in Newark DE!

Draft budget plan proposes deep cuts across federal health programs A draft budget proposal circulating among federal officials would dramatically deepen cuts at the nation's top health agency, eliminating some public health programs entirely and serving as a roadmap ...

New AP story about HHS passback budget and NIH reorganization.

www.newsday.com/news/nation/...

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Finally, I am happy to say that I am trying to relocate to @bsky.app after a science social media hiatus. Looking forward to reconnect with you here. Please follow us if you find our work on protein folding interesting! 9/9

We have benefitted immensely from collaboration with Ed O'Brien, and this project was spearheaded by the remarkable team of Yang Jiang and
@friedlab.bsky.social's April Xia. Thanks to NSF and NIH for their support of this work. 8/9

To summarize, we think that entangled states represent a class of misfolding that can explain complex refolding kinetics & why some proteins do not refold efficiently. Since they are not easily caught by chaperones, they may pose dangers to our cells too. 7/9

We also used two types of structural mass spectrometry, LiP-MS and XL-MS, to characterize the topologically misfolded form of PGK and showed that these features match the entangled conformations from simulations quite well. 6/9

We showed this in a few ways. First, Yang ran extensive simulations on PGK, showing it gets entangled, and if you take the trajectories away with entanglements the stretched exponential signature also disappears. 5/9

But if this is true, what are these various non-native states that cannot just sort themselves out and get back on the normal folding path? We think they are "entangled states," or conformations with non-covalent lasso entanglements. 4/9

Physically, this could correspond to a scenario of a rough free energy landscape with many non-native minima that do not easily interconvert and which have a diverse spectrum of rate constants. 3/9

Where do we begin? In the late 90s, protein folders noticed that not all proteins fold with expected single-exponential kinetics. The enzyme from glycolysis, PGK, appears to follow a stretched exponential function instead. 2/9

Protein misfolding involving entanglements provides a structural explanation for the origin of stretched-exponential refolding kinetics Protein misfolding involving entanglements could be the structural origin of power-law distributions of folding times.

Excited to share some work in our collaboration between @fried_lab and Ed O'Brien @psu_chemistry, just published in @ScienceAdvances :
www.science.org/doi/10.1126/.... Here we describe the structural basis for stretched exponential kinetics in protein folding. A thread.

Hey #proteinfolding #biophysics #TeamMassSpec #proteomics people: After a long social media hiatus, @friedlab.bsky.social is back on @bsky.app. Looking forward to connecting with you all in this space, and filling my day with less alt-right/crypto/AI-nonsense!