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Ezequiel Galpern

@eag91.bsky.social
286 followers 1.1K following 29 posts

‪MSCA fellow at @crg.eu‬ w/M. Dias and @jonnyfrazer.bsky.social > Biological Physics | Proteins | Comp Bio | ML scholar.google.com/citations?user=n…

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Ezequiel Galpern @eag91.bsky.social · 25/09/2026
📊 Bigger is not necessarily better. Across ProteinGym benchmarks, scaling protein language models does not consistently improve zero-shot fitness prediction. We discuss why model likelihood is not the same as fitness, and what may be limiting performance.
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Ezequiel Galpern @eag91.bsky.social · 08/08/2026
🚨 Paid MSc research opportunity at CRG Barcelona! With Mafalda Dias and @jonnyfrazer.bsky.social, we’re hosting a 4-month MSc project: 🧬 “Folding versus function: disentangling the molecular mechanisms of missense variants in gene-trait associations” More info 👇 www.crg.eu/en/content/t...
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Ezequiel Galpern @eag91.bsky.social · 05/08/2026
3/ The AWSEM–IF blends improve global ΔΔG prediction and reduce the systematic bias of inverse-folding models at functional sites.
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Ezequiel Galpern @eag91.bsky.social · 05/08/2026
2/ Our starting point: inverse-folding models predict stability changes surprisingly well, but they can confuse functional conservation with structural stability. We blend them with the physics-based AWSEM potential to combine complementary signals.
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Ezequiel Galpern @eag91.bsky.social · 03/03/2026
elixir-europe.org/events/3d-bi... Next week!
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Ezequiel Galpern @eag91.bsky.social · 06/11/2025
Our method for predicting folding dynamics/mechanisms from sequence info is now a book chapter! link.springer.com/book/9781071... @diegulise.bsky.social
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Ezequiel Galpern @eag91.bsky.social · 12/08/2025
Some sites have, on average over all the possible variants, high Dark Energy. In those cases, there is a function beyond protein folding affecting natural selection. This is clearly the case of Enzyme catalytic sites
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Ezequiel Galpern @eag91.bsky.social · 12/08/2025
The idea is simple. For a deleterious mutation, we expect the protein to get destabilized. But how much? Correlations between a ΔΔG DMS and the corresponding ESM-2 scores are not perfect. We define the difference between these two free energies as a ‘Dark Energy’.
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Ezequiel Galpern @eag91.bsky.social · 15/07/2025
Also, we show that both the stability and cooperativity changes induced by mutations can be computed directly using sequence-based evolutionary models. 6/n
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Ezequiel Galpern @eag91.bsky.social · 15/07/2025
Protein topology imposes limits on the variability of folding cooperativity within a family. While most beta and alpha/beta structures exhibit only a few possible mechanisms despite high sequence diversity, alpha topologies allow for diverse folding scenarios. 5/n
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Ezequiel Galpern @eag91.bsky.social · 15/07/2025
For 15 diverse protein families, we computed the folding mechanisms of hundreds of proteins by simulating an Ising chain of folding elements, or foldons. The energetics is determined by each amino acid sequence. 4/n
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Ezequiel Galpern @eag91.bsky.social · 15/07/2025
We show that it is possible to use sequence info to go beyond predicting native structures and global stability to infer the folding mechanisms of globular proteins. We mapped a Potts evolutionary energy at the amino-acid level to a coarse-grained description of folding. 3/n
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