iiinova — where your digital self keeps evolving

Green Ahn @greenahn.bsky.social · 01/10/2025

I’m extremely fortunate to work with a fantastic team - Shayan Sadre, Ella Haefner, and Brian Coventry and all authors at @uwproteindesign.bsky.social with support from David Baker. This work would not have been possible without them!

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Green Ahn @greenahn.bsky.social · 01/10/2025

Programmable pH-sensitivity enables building conditional control into protein-based therapeutics, diagnostics, and synthetic biology tools.

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Green Ahn @greenahn.bsky.social · 01/10/2025

These methods identified key principles for designing pH sensitivity, enabling the development of pH-dependent binders against several disease-relevant targets and their application in catalytic extracellular protein degradation.

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Green Ahn @greenahn.bsky.social · 01/10/2025

and (ii) engineer buried charged networks inside the binder to destabilize the binder while preserving the interface residues.

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Green Ahn @greenahn.bsky.social · 01/10/2025

We combined Rosetta and deep-learning based methods to (i) weaken the binder-target interface by inducing electrostatic repulsion upon histidine protonation

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Green Ahn @greenahn.bsky.social · 01/10/2025

pH gradients are central to physiology, from vesicle acidification to the acidic tumor microenvironment. But how do we program proteins to respond to pH? In our new preprint biorxiv.org/content/10.110…, we developed computational methods to rationally design pH-sensitive binders. 🧵

biorxiv.org

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Reposted by Green Ahn

Science Magazine @science.org · 18/02/2025

New research in Science represents a notable step forward in designing enzymes from scratch. With a new approach, researchers designed an enzyme that uses a covalent intermediate to catalyze a two-step reaction, analogous to what many proteases do when breaking apart proteins. scim.ag/41kZBOI

scim.ag

Computational design of serine hydrolases

The design of enzymes with complex active sites that mediate multistep reactions remains an outstanding challenge. With serine hydrolases as a model system, we combined the generative capabilities of ...

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