Happy to share our work on conventional and time-resolved cryo-EM studies of NTSR1, now published in Nature!
nature.com/articles/s41...
Wonderful collab. w/ Sumino, Mitsutake, Kobilka, & Inoue labs.
Congrats to Kazuhiro, Kouki, Toshiki, Shun & everyone involved!
*Electron crystallography, not microscopy
In situ Cryo-EM: study proteins in physiological environment!
Started this project years ago, but now everything is deposited on @addgene.bsky.social and a short @protocolsio.bsky.social is online. Try it out to make your own (cheap) homemade nuclease/Benzonase!
dx.doi.org/10.17504/protocols.io.261ged7xov47/v2
Thank you @jcoker10.bsky.social and Michael Lim!
3) if you want more diversity in your predictions, try different charges and ligand representations.
Read the full text here: biorxiv.org/content/10.6... (6/6)
The main takeaways are: 1) identical results not depending on the input formats should be ensured, 2) inclusion of protonation-related steps into training and inference should improve things (amino and carboxy groups are ubiquitous in PDB!), (5/6)
The same for acetate and acetic acid (the protein is more challenging given that no experimental structure is available and that the acetic acid probably binds in the protonated form) (4/6)
Ligand positions are affected by the input format (3/6)
Same for carboxylates (acetate and acetic acid) (2/6)
New preprint: We checked whether AlphaFold and its great freely available analogs (including the recent Protenix) can predict the effects of ligand charge. Surprisingly, the predictions sometimes depended on the input format stronger than on the charge! (1/6)
Influence of molecular representation and charge on protein-ligand structural predictions by popular co-folding methods [new]
Input format impacts pred's more than protonation. Consistency & protonation steps vital for model improv.
This visualization style reminded me of black fungi
First learned about SeqHub from this nice interview with Yunha Hwang www.youtube.com/watch?v=w6L9...
I found it very interesting to surf gene neighborhoods of homologs to the proteins we study
A ligand-binding sensor domain got a tiny insertion from cytochrome c, which contained a heme-binding motif, and now it is a nitric oxide sensor. As simple as that: www.biorxiv.org/content/10.6...
We're launching a research lab at SMART. Shenzhen Medical Academy for Research and Translation is a newly established institute with long-term funding mechanisms for internal and external investigators. At full capacity SMART aims to support up to 400 labs.
www.scmp.com/news/china/s...
I recorded ~8h introducing the main algorithms for protein design: from classical approaches to protein language models, AlphaFold, ESMFold, MPNN, diffusion models and more :)
youtu.be/wKUYtAt87d4T...
Slides
drive.google.com/file/d/1EPLj...
English is available only via auto-translated subtitles
The bureaucracy of science has grown so much, the system is collapsing upon itself:
Scientists have become administrators of grants rather than spending time on science.
Paid administrators are demanding even more administrative work from scientists.
Administrators are eating the science budget.
I’ve recorded ~8h explaining the architectures of AlphaFold, AF2 & AF3, as well as the context needed to understand their development, applications and limitations :)
youtu.be/_jDRr5BcTaY
Slides
drive.google.com/file/d/1i4QE...
English is available only via auto-translated subtitles
Great to see a nice computational study also complemented by experiments, and impressive that the approach works overall!
As the year winds down, I hope you all get the chance to slow down, spend time with family and loved ones, and enjoy the simple moments. I wish you a warm and peaceful holiday season 💫
Four years ago, the red-light–activated channelrhodopsin #Chrimson restored basic vision in a blind patient. Here, we uncover its #multicolor_photoreactions and show implications for optogenetic applications. Many interesting details and a wonderful team🥳! www.pnas.org/doi/10.1073/...
Given the "positive inside" rule, many membrane proteins could potentially interact with negatively charged nucleic acids - I wonder if anyone done a whole proteome analysis
very unusual - a tRNA regulated anion channel
Bacteriorhodopsin is not from bacteria 😅
Cryo-EM structure of sensor histidine kinase QseE with its activator QseG. Once again AlphaFold produced great model for the complex before the experimental data were available! doi.org/10.1128/mbio...
Hall of Fame for unexpected Boltz predictions, by Pavel Shishkin
Joys of correcting proofs
We got a large Helmholtz Bioengineering grant with Oliver Daumke, Artur Yakimovich, Alina Bazarova, and Dietrich Ruess to use protein design to target cancer.
Five open postdoctoral positions in Generative AI & Protein Engineering. Share & apply!
jobrxiv.org/job/max-delb...
