Also, check out the complementary preprint from @lindorfflarsen.bsky.socialwww.biorxiv.org/content/10.1...

Prediction of phase separation propensities of disordered proteins from sequence

bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

This opens the door to the design of precise IDR-associated mutations that may fall outside of canonical binding motifs but will still enhance/suppress intermolecular interaction.

Finally, we see this approach as complementary to existing computational methods (structure prediction, simulations, sequence feature analysis, etc.) rather than replacing any of those. It fills a gap we need, and we hope it will be useful to others.

There are lots of caveats and limitations associated with this, and we encourage folks to consider those, but we also think this offers a way to build hypotheses and explain extant data. Predictions can be made over at finches-online.com

Much more exciting to me is our ability to predict heterotypic interaction between two IDRs (or an IDR and a folded domain surface) with residue resolution, making it simple to build testable hypotheses as to how an IDR may interact with a partner

This approach allows us to do a few things. One of these is we can (qualitatively; lots of caveats) predict full phase diagrams from sequence

We have a second paper for doing exactly this! We don’t talk about it much in the preprint but you can design IDRs with requested Rg or Re values in a single line of code! www.biorxiv.org/content/10.1...

Sequence-ensemble-function relationships for disordered proteins in live cells

bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

I mocked up the logo from "memory"; might pitch it to NPG and see what they say...

Relevant links: Pappu/Gladfelter labs' work on dynamical arrest (beautiful story) dx.doi.org/10.1038/s414...dx.doi.org/10.1016/j.de...

Given recent elegant work from Pappu lab on how arrested dynamics can give rise to coexisting condensates and previous work on the material states of Drosophila germ granules during development, I wonder how much of this layering is driven by dynamical arrest as opposed to equilibrium biases...