Discover and read the best of Twitter Threads about #AlphaFold

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Systematically overlaying likely pathogenic variants over @DeepMind #AlphaFold predicted structures provides a unique opportunity to dive into the mechanisms of disease.

Here, NOD2 inflammatory disease-causing variants on the experimentally unresolved structure. 1/5
Data-wise, the @OpenTargets Platform and Genetics Portal provide a comprehensive aggregation of disease-causing variants post-processed from other great resources like @GWASCatalog or @NCBI_Clinical ClinVar (via @evarchive) among others…
Now we also make human #AlphaFold structures available as a result of the collaboration between @embl and @DeepMind. All thanks to the great protein annotation tools provided by @uniprot

See NOD2 platform profile page…
Read 5 tweets
Since the publication of #AlphaFold2 and #RoseTTAFold and now that the tools and models have been made accessible, there has been an avalanche of attempts to solve old crystal structures. This thread covers tips from the #PhaserTeam for doing #MR with these models. (1/...)
The first thing to be aware of is that the B-factor fields contain measures of confidence in the correctness of the prediction, not actual B-factors. This means: 1) we can use that confidence to trim the model and 2) we need to convert that to an appropriate B-factor. (2/...)
Phaser will take those B-factors and use them to weight the different parts of the model. This can improve your chances of success with the model. (3/...)
Read 11 tweets
Very excited to share that our work on Protein Nonrefoldability is out today in @J_A_C_S! #AlphaFold might be great at finding proteins' native structures... but turns out many proteins themselves are not! Short 🧵1/7…
We developed a mass spec approach to probe the refoldability of the proteome. First we unfold & refold E. coli extracts, then use a protease to interrogate the structures of 'refolded' proteins. The resulting peptide fragments are sequenced by LC-MS & compared to native. 2/7
We found that most simple 'model' proteins are well-behaved and can refold on their own. But lots of multi-subunit assemblies, multi-domain proteins, and certain fold-types cannot fully refold intrinsically. 3/7
Read 7 tweets
Now that the #alphafold hype has completely died down (ha!), I've written a new blog post on the AF2 method paper:…. This is a technical deep-dive into aspects of AF2 that I find most surprising/innovative and of relevance to broader biomolecular modeling.
My post is _not_ a high-level summary of how AF2 works. For that I suggest @c_outeiral's blog post….
Should say that we will have in a couple of weeks a formal review paper out that is a high-level overview of AF2 and its implications.
Read 3 tweets
Yesterday we announced early collaborations using the #AlphaFold Protein Structure Database, which offers the most complete and accurate picture of the human proteome to date. So how is AlphaFold helping these organisations with their work…? 1/ Image
The Drugs for Neglected Diseases initiative (@DNDi) has advanced their research into life-saving cures for diseases that disproportionately affect the poorer parts of the world. 2/ Image
The @CEI_UoP is using #AlphaFold's predictions to help engineer faster enzymes for recycling some of our most polluting single-use plastics. 3/ Image
Read 4 tweets
A personal view point on the #AlphaFold announcement today from the @DeepMind and @emblebi team, part of @embl. TL;DR - I am *still* pinching myself about this.
When @demishassabis and the AlphaFold team first presented the results from CASP to me last November I genuinely almost fell off my chair. I think I swore quite a bit (in a British way) in amazement.
One of the reasons was I knew how rigorous CASP was - 20 years ago people published all sorts of "solving the folding problem" which then... didn't work beyond the training set. CASP cleverly used the fact that there are genuinely unknown structures each year solved by experiment
Read 15 tweets
Thoughts on the #AlphaFold #Deepmind 'we done the proteome' news:
(1) This is great.
(2) This was always going to happen. I'm surprised they did it this fast, but cool.
(3) The dataset will be invaluable for hypothesis generation.
(4) Hypotheses will still need to be proven at the lab bench.
(5) This will advance structural biology, allowing phasing of MX datasets and tracing of domains/proteins into EM maps.
(6) I'm interested to see how their models perform with drug & biologic design.
(7) I'm interested to see how their model aid in construct design. Knowing disordered/unstructured regions is super important for designing well behaved, soluble recombinant proteins for structural study. #Alphafold
Read 18 tweets
Today with @emblebi, we're launching the #AlphaFold Protein Structure Database, which offers the most complete and accurate picture of the human proteome, doubling humanity’s accumulated knowledge of high-accuracy human protein structures - for free: 1/
We’re also sharing the proteomes of 20 other biologically-significant organisms, totalling over 350k structures. Soon we plan to expand to over 100 million, covering almost every sequenced protein known to science & the @uniprot reference database. 2/
We’re excited to see how this will enable and accelerate research for scientists around the world. We've already seen promising signals from early collaborators using #AlphaFold in their own work, including @DNDi, @CEI_UoP, @UCSF & @CUBoulder:… 3/
Read 5 tweets
Daily Bookmarks to GAVNet 07/16/2021…
How Many Numbers Exist? Infinity Proof Moves Math Closer to an Answer.…

#numbers #mathematics #InfinityProof
Read 8 tweets
Yesterday we shared the news that #AlphaFold has been recognised as a solution to the ‘protein folding problem’ by #CASP14, the biennial Critical Assessment of Protein Structure Prediction. But what exactly is protein folding, and why is it important? A thread… (1/6)
Proteins are the building blocks of life - they underpin the biological processes in every living thing. If you could unravel a protein you would see that it’s like a string of beads made of a sequence of different chemicals known as amino acids. (2/6)
Interactions between these amino acids make the protein fold, as it finds its shape out of almost limitless possibilities. For decades, scientists have been trying to find a method to reliably determine a protein’s structure just from its sequence of amino acids. (3/6)
Read 6 tweets
#Alphafold by #deepmind used solid interdisciplinary intuitions for algorithm/model design. It wasn't just a rinse-and-repeat machine learning exercise. Details on methods are limited, but here's my best interpretation (+some predictions) so far: [1/n]
Protein sequence databases provide us samples that have defacto passed the fitness test of evolution and are information-rich. "Genetics search" is a retrieval step to find nearest-neighbors as defined by sequence alignment. Why do we need nearest-neighbors (NNs), you ask?
There's a neat principle/intuition called coevolution that can help explain. The mutational variance observed can give clues to protein structure and function. Read more here:
Read 13 tweets
Thrilled to announce our first major breakthrough in applying AI to a grand challenge in science. #AlphaFold has been validated as a solution to the ‘protein folding problem’ & we hope it will have a big impact on disease understanding and drug discovery:
The ultimate vision behind @DeepMind has always been to build AI and then use it to help further our knowledge about the world around us by accelerating the pace of scientific discovery. For us #AlphaFold represents an exciting first proof point of that thesis.
Congratulations to the whole #AlphaFold team! And thanks to John Moult and the fantastic CASP organisers and community for championing this critical problem and creating such an amazing benchmark - it really is the gold standard for scientific assessment. #CASP14
Read 3 tweets
In a major scientific breakthrough, the latest version of #AlphaFold has been recognised as a solution to one of biology's grand challenges - the “protein folding problem”. It was validated today at #CASP14, the biennial Critical Assessment of protein Structure Prediction (1/3)
CASP is both the gold standard for assessing predictive techniques and a unique global community built on shared endeavour. Accuracy is measured on a range of 0-100 “GDT”. #AlphaFold has a median score of 92.4 GDT across all targets - its average error about the width of an atom.
We’re excited about the potential impact #AlphaFold may have on the future of biological research and scientific discovery. Thank you to the CASP organisers & the whole community - we look forward to the many years of hard work and discovery ahead:
Read 3 tweets
Join us this afternoon for the AI & Molecular World track at #AMLD2020 @appliedlmdays, 1.30pm-5pm, Room 1A
Organised with @FreyrSverrisson @TheophileGaudin @pgainza and @befcorreia.

Thrilled to have such a brilliant set of speakers this year ⬇️: Image
@FreyrSverrisson @TheophileGaudin @pgainza @befcorreia The first part will feature Jennifer Listgarten (@jlistgarten, @UCBerkeley), Amina Mollaysa (@unige_en), Tess Smidt (@tesssmidt, @BerkeleyLab) and Michele Ceriotti (@MicheleCeriotti , @COSMO_EPFL). Image
@FreyrSverrisson @TheophileGaudin @pgainza @befcorreia @jlistgarten @UCBerkeley @unige_en @tesssmidt @BerkeleyLab @MicheleCeriotti @COSMO_EPFL After the coffee break, we will continue at 3.30pm with Andrew Senior (#AlphaFold, @DeepMind), Katerina Vriza (@kvriza, @LC_Mater_Design) and last, but not least Katya Putintseva (@goneblotting, @labgeni_us). Looking forward! Image
Read 3 tweets
✨💡 This is an ace idea from @sarah_edo! 💕

👩‍💻 Be on the lookout for a @TensorFlow Advent Calendar tomorrow, as well, highlighting meaningful, high-impact projects and papers from our community. If you'd like for yours to be considered, please shoot me an @-mention!
#TFadvent begins today! 😄

For our first project, I'd like to highlight this accessibility example from @shekitup that uses @TensorFlowJS to interpret sign language—and then translates those signs into input that can be used by a home assistant! 🗣️✨…
🎁 Day #2 of #TFadvent:

🤖 Check out this project from a recent hackathon at @ColbyCollege! The team trained a @TensorFlow model to learn muscle movements, then used that model to send signals to a prosthetic arm, controlling one finger at a time. ✨

Read 32 tweets

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