@alexholehouse
Associate Prof. at WashU School of Medicine; biophysics/biochem/evolution of intrinsically disordered proteins. How does nature encode function without a stable structure? We work in vivo / in vitro / in silico. He/him. https://www.holehouselab.com/
The Protein Data Bank (#PDB) has reached a new milestone: 250,441 entries in the archive, a record since its founding in 1971, all thanks to the efforts and contributions of the structural biology community.
⬇️ more ⬇️
www.wwpdb.org/news/news?ye...
#StructuralBiology
IDPSeminars is back TOMORROW! Come see @tanjamittag.bsky.social and @xsalvatella1.bsky.social ! Not to be missed!!
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New (well, very old, but 100% updated) preprint:
Rational design of disordered proteins for systematic sequence-to-function investigation
Work done in collaboration with @shaharsu.bsky.social lab - check out the three (3) threads from the folks who did the work!
On the cover of #JCP, Pablo’s work on “Condensate Deborah Numbers”
pubs.aip.org/aip/jcp/arti...
Also, check out collaborative work from @thedrakejensen.bsky.social (Sunday poster B118), @albertymh.bsky.social (Sunday poster LB44), Ella Mozier (Sunday poster B336), and Shraddha KC (Monday poster B110)! (7/7)
Wednesday, Feb 25th: @jefflotthammer.bsky.social will present a poster on RAVEN, expanding on content from his talk (Poster B26). (6/7)
Monday, Feb 23rd: @jefflotthammer.bsky.social will present a platform talk on our new IDR-specific protein-language model, RAVEN, in the Protein Structure Prediction and Design (9:15 AM, Rooms 201/202/203). (5/7)
Sunday, Feb 22nd: @idpemery.bsky.social will present a poster on his work using integrative biophysical techniques to understand the disordered region in the BMAL1 transcription factor in the context of circadian regulation (Poster B119). (4/7)
Sunday, Feb 22nd: Nick Razo will present a poster on our work using protein language models to extract functional/evolutionary information directly from sequence embeddings (Poster B113). (3/7)
Sunday, Feb 22nd: @bornanovak.bsky.social will present a poster on STARLING, our deep learning tool for predicting disordered protein ensembles (Poster B112). (2/7)
Sad to miss my first Biophysical Society Meeting in 12 years, but the lab will have strong representation! A thread (1/7)
You know… I’m not sure! Now you mention it we had to remove our FINCHES logo from that paper last year, and obviously we had to explicitly get your permission to use Marv at all… but no one questioned the inclusion of a logo? How weird? Maybe policy has changed?
If @shaharsu.bsky.social had his way 😂
Try it now, either with
pip install idptools-starling
or, if pip install sounds like instructions for planting an apple, try our colab notebook instead colab.research.google.com/github/idpto...
While the core ideas remain the same as the preprint, basically EVERYTHING in this version is new, including a completely new model and model architecture, integrated Bayesian re-weighting for experimental biasing, a conformation-aware embedding model, ionic strength conditioning, and more.
STARLING is a deep learning model that lets you easily and rapidly predict coarse-grained ensembles of disordered regions. In effect, it lets you build structural models of sequence-dependent ensembles for your favourite disordered region.
Papers are like buses... You wait for ages, then two come along at once.
Huge congrats to @bornanovak.bsky.social and @jefflotthammer.bsky.social for pushing and driving every aspect of this work, preprinted ~1 year ago to the day (Friday before BPS), now published!
www.nature.com/articles/s41...
lol that I would not agree with 😆
BUT, all that said, MANY MANY questions remain to be answered in this system (and we're trying!!! the work continues!!) - I too would want molecular, mechanistic insight into what's going on here!
Practically, I think it also says that motif-based host/guest tests are insufficient to claim the presence of a "true" motif (i.e., a region that enables site-specific binding - maybe not the right definition of motif?) without ALSO testing shuffling/distributing disrupts interaction/function.
Conceptually, I think this is useful to consider because it may change what one might expect conservation to look like (or not, if this was already obvious, which to many it might have been 😅).
I do think what this work offers by way of a general principle is that just because an IDR interacts via a motif need not *necessarily* mean motif-based interactions are the only way it can interact, nor is the presence of such a motif necessarily sufficient for interaction.
Thanks, Andrea - going to be super brief before I dive into a day of meetings, but just to say I don't disagree at all when general principles need to be predictive of specific instances (which is unambiguously the most useful type of prediction!).
Also, check out the beautiful news & views from Yu-Xi Xiao and Alan Moses!
www.nature.com/articles/s41...
Finally, our editor @djdavid.bsky.social was an absolute mensch from start to finish. Fair and supportive, gave us extra time when we needed it, and worked with us to get this to where it is today. An absolute pleasure; I would HIGHLY recommend folks consider NCM for future work. We certainly will!
While the enterprise of science publishing gets a lot of slack, the humans involved at the science level are largely excellent. All the reviewers of this paper really improved it. We are indebted to our colleagues for taking the time and effort to engage deeply and constructively with our work.
Pleased to share the final version of this behemoth of a paper, now finally published. I guess I can retire now?
www.nature.com/articles/s41...
More functional data, many thousands of words removed, and a few other updates from last year's preprint.
Many condensates can be described as active soft materials that generate molecular fluxes. Here we develop a new #nonequilibrium approach (TRACE) to study molecular transport through condensates! Work led by Yashraj Wani!!
www.biorxiv.org/content/10.6...