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Ezequiel Galpern

@eag91.bsky.social

210 followers 1.1K following 11 posts

‪MSCA fellow at @crg.eu‬ w/M. Dias and @jonnyfrazer.bsky.social > Biological Physics | Proteins | Comp Bio | ML https://scholar.google.com/citations?user=n55NtEsAAAAJ&hl=en

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Ezequiel Galpern @eag91.bsky.social · Aug 12

Dark Energy is not a relative score, but provides a common scale and has physical energy units. And it can be also computed even if ΔΔG is not available, using AWSEM force-field. You can compute it for your favorite PDB colab.research.google.com/github/eagalpern/colabs/blob/main/DarkEnergy.ipynb

colab.research.google.com

Ezequiel Galpern @eag91.bsky.social · Aug 12

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

Ezequiel Galpern @eag91.bsky.social · Aug 12

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’.

Ezequiel Galpern @eag91.bsky.social · Aug 12

❗New Preprint w/ C Bueno (‪@cabb99.bsky.social‬), IE Sánchez (@nachoquique.bsky.social‬), PG Wolynes & DU Ferreiro (@diegulise.bsky.social‬)

We define the Protein Dark Energy and use it to localize and quantify the functional evolutionary constraints on natural proteins

arxiv.org/abs/2508.08109

Probing the Dark Energy in the Functional Protein Universe

We show how to localize and quantify the functional evolutionary constraints on natural proteins. The method compares the perturbations caused by local sequence variants to the energetics of the prote...

Ezequiel Galpern @eag91.bsky.social · Jul 15

And you can make folding mechanism predictions for your favorite protein!
colab.research.google.com/github/eagal...

colab.research.google.com

Ezequiel Galpern @eag91.bsky.social · Jul 15

Also, we show that both the stability and cooperativity changes induced by mutations can be computed directly using sequence-based evolutionary models.
6/n

Ezequiel Galpern @eag91.bsky.social · Jul 15

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

Ezequiel Galpern @eag91.bsky.social · Jul 15

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

Ezequiel Galpern @eag91.bsky.social · Jul 15

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

Ezequiel Galpern @eag91.bsky.social · Jul 15

We know that closely related proteins usually share similar three-dimensional structures. But differences in their amino acid sequences can lead to distinct folding mechanisms, enabling the natural evolution of diverse biological functions.
2/n

Ezequiel Galpern @eag91.bsky.social · Jul 15

Finally published!
“Inferring protein folding mechanisms from natural sequence diversity”

Open acces link: authors.elsevier.com/a/1lQvh1SPTB...
@biophysj.bsky.social

A new chapter of an amazing project w/ @diegulise.bsky.social and Ernesto Roman

1/n

authors.elsevier.com

Reposted by Ezequiel Galpern

Martin Ezequiel Farina @profe-hallucigenia.bsky.social · Mar 9

Investigadores que estudian el universo desde Argentina. Mi colaboración de hoy para Viva www.clarin.com/viva/detecti...

Los detectives espaciales que desde Argentina buscan entender el Universo

Se destacan en radioastronomía, astrobiología, física y geología planetaria. Quiénes son los científicos locales que buscan descifrar el Cosmos.

Reposted by Ezequiel Galpern

Nacho Sánchez @nachoquique.bsky.social · Jan 13

En ciencia no hay preguntas pequeñas, pero igualmente divierte investigar con @diegulise.bsky.social y Ezequiel Galpern por qué hay 20 aminoácidos en las proteínas y 4 nucleótidos en el ARN doi.org/10.1590/SciE...

Why are there 20 amino acids and 4 nucleotides?

Evolution of folded biopolymers requires effective and fast search of both the conformational space for folding and the sequence space for evolution. Molecular information theory and energy landscape theory show that the alphabet size of extant proteins and RNA is just enough to fulfill these requirements, given the constraints posed by the chemical physics of these polymers. Empirical estimations of the size of the effective sequence and conformational spaces of natural biopolymers support the theoretical predictions.