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Fried Lab JHU

@friedlab.bsky.social

Asst. Prof of Chemistry🧪 & Biophysics 🧬 at JohnsHopkins; unofficial lab rabbi ✡️; ally 🏳️‍🌈; #TeamMassSpec. PI of structural proteomics/protein folding/ageing research lab.

Posts Replies Media

Fried Lab JHU @friedlab.bsky.social · 30/05/2025

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!

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Fried Lab JHU @friedlab.bsky.social · 27/03/2025

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

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Fried Lab JHU @friedlab.bsky.social · 27/03/2025

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

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Fried Lab JHU @friedlab.bsky.social · 27/03/2025

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

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Fried Lab JHU @friedlab.bsky.social · 27/03/2025

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

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Fried Lab JHU @friedlab.bsky.social · 27/03/2025

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

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