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GAMA Miguel Angel @miangoar.bsky.social · 21d

I'm not sure. LinkedIn makes me cringe, it feels so inorganic to me. On the other hand, my Twitter algorithm recommends really good stuff about proteins, microbes, and AI. In contrast, the algorithm of 🦋 is bad :( and the good content (I.e. Science) mostly comes from reposts by our colleagues.

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Reposted by GAMA Miguel Angel

Claudia Alvarez Carreño @claudiaalcar.bsky.social · 24d

Happy to share Piecing Together the History of Protein Folds From a Fragmented Evolutionary Record 🧪
It appears as part of a Special Section in @genomebiolevol.bsky.social organized by @cpuentelelievre.bsky.social @proteinmechanic.bsky.social and J. Douglas

doi.org/10.1093/gbe/...

Piecing Together the History of Protein Folds From a Fragmented Evolutionary Record

Abstract. Protein folds are structural units defined by the number, type, arrangement, and orientation of their core secondary structural elements. The uni

doi.org

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Reposted by GAMA Miguel Angel

Paco Barona Gomez @evodivmet.bsky.social · 27d

🫡

Ákos T Kovács @evolvedbiofilm.bsky.social · 27d

The cycad coralloid root: is there evidence for plant-microbe coevolution?

#CurrOpinMicro by Kimber Zonneveld, Edder Bustos-Diaz, @evodivmet.bsky.social, Angelica Cibrian-Jaramillo

@naturalis.bsky.social & #LeidenBiology @leidenscience.bsky.social cooperation

www.sciencedirect.com/science/arti...

The cycad coralloid root: is there evidence for plant-microbe coevolution?

Cycads are survivors, ancient plants originating in the Carboniferous. We hypothesize that cycad resilience and recent diversification could be partia…

www.sciencedirect.com

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Reposted by GAMA Miguel Angel

Sam Berry @sberry.bsky.social · Aug 26

This is a very cool ancestral reconstruction study by @krishnareddy.bsky.social et al. that I recommend reading! @rachellegaudet.bsky.social and I thought it was so interesting that we wrote a News & Views about it, check it out: rdcu.be/eCfyl

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Reposted by GAMA Miguel Angel

Kevin K. Yang 楊凱筌 @kevinkaichuang.bsky.social · 25d

If you're an undergrad and want to intern with me, this is where you need to apply!

Microsoft Research @msftresearch.bsky.social · 26d

The Microsoft Research Undergraduate Internship Program offers 12-week internships in our Redmond, NYC, or New England labs for rising juniors and seniors who are passionate about technology. Apply by October 6: msft.it/6015scgSJ

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Reposted by GAMA Miguel Angel

Stephanie Wankowicz @stephanieaw.bsky.social · 27d

Structural bioinformatics is incredibly powerful on its own or when paired with theory or experiment. One of the PDB's superpowers isn’t from one structure, but comparing many to uncover folds, binding sites, and subtle conformational shifts. chemrxiv.org/engage/chemr...

10 Rules for a Structural Bioinformatic Analysis

The Protein Data Bank (PDB) is one of the richest open‑source repositories in biology, housing over 277,000 macromolecular structural models alongside much of the experimental data that underpins thes...

chemrxiv.org

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GAMA Miguel Angel @miangoar.bsky.social · Sep 5

This is a breakthrough for protein science🔥AFAIK this is the largest protein DB, with >100B seqs (3B clustered at 50%). New biology will come from LOGAN: new folds, topologies, etc. You can also improve your AlphaFold models by building better MSAs. Future AI models will also use LOGAN for training

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Reposted by GAMA Miguel Angel

Rayan Chikhi @rayanchikhi.bsky.social · Sep 3

🌎👩‍🔬 For 15+ years biology has accumulated petabytes (million gigabytes) of🧬DNA sequencing data🧬 from the far reaches of our planet.🦠🍄🌵

Logan now democratizes efficient access to the world’s most comprehensive genetics dataset. Free and open.

doi.org/10.1101/2024...

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

13/13

BindCraft
nature.com/articles/s41...

A recent conference about BindCraft
youtube.com/watch?v=qQih...

Boltzdesign1
www.biorxiv.org/content/10.1...

One-shot design of functional protein binders with BindCraft - Nature

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity wit...

nature.com

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

12/13 Bindcraft started as a binder design tutorial for the Boston Protein Design and Modeling Club, and it evolved into one of the most promising tools in AI-based protein design. And Importantly, it is open-source!🤗

Congrats to all the authors!

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

11/13 The authors have gone a step further and are currently developing BoltzDesign1, which instead of designing binders, focuses on biomolecular interactions between proteins and small molecules. However, one of the main limitations of both AIs is their high computational cost.

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

10/13 Bindcraft’s capabilities have also been validated by other labs and, perhaps most notably, in an international binder design competition organized by a company called AdaptyvBio, where Bindcraft won.
adaptyvbio.com/blog/po104

Adaptyv Bio - Protein Design Competition: Has binder design been solved?

We analyze the results of our protein design competition where 130 designers created binders for EGFR. With a 5x improvement in success rates and some designs outperforming clinical antibodies, we exp...

adaptyvbio.com

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

9/13 the most important results IMO was the determination of atomic structures of four binders, where in all cases, the computational designs were highly consistent with the experimentally determined ones.

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

8/13 They designed binders targeting:
*proteins with no known binding sites
*membrane proteins , which are much harder than intra/extra-cellular proteins
*proteins lacking evolutionary information
*proteins that interact with DNA/RNA
*medically relevant proteins such as those causing allergies

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

7/13 Then it uses ProteinMPNN to optimize for solubility, increasing the chances of experimental success. Finally, uses AF2 to predict the structure. To demonstrate Bindcraft’s utility, the authors carried out many wet-lab experiments, something not as common as I would like.

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

6/13 Bindcraft takes advantage of this by first proposing a random seq and predicting its structure to assess how well it interacts with the target protein. It then uses info from each interaction, successful or not, to optimize the seqs until it arrives at a credible interaction

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

5/13 Bindcraft is an improved version of AlphaFold2, specifically AF-Multimer, which predicts the structure of protein complexes. Having been trained on thousands of structures, AF-Multimer learned to identify which sites are most likely to form protein–protein interactions.

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

4/13 Bindcraft designs both the sequence and structure of binders, achieving a success rate between 10-100%, since designing large or complex binders is more challenging. This is enormous, considering that our previous best physics/biochemistry-based methods reached a 0.1%.

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

3/13 We have learned how to design PPI so that one protein, called a binder, can bind to another and regulate it. e.g., cancer drugs are binders. However, designing binders requires yrs of research and detailed biomolecular knowledge. So, what if we teach an AI to design binders?

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

2/13 Proteins carry out many functions on their own, but when they interact with each other, they generate a diversity of mechanisms that expand and regulate those functions. PPI arose over millions of years of evolution, giving rise to processes as complex as metabolism.

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

1/13 🧵 Today, Bindcraft was published in
@nature.com , one of the most famous AIs in biology for designing protein–protein interactions (PPI). In my opinion. Bindcraft represents one of the most important advances in the post–AlphaFold2 era.

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

"We find that the ECOD and CATH provide the most extensive structural coverage of the PDB. ECOD and SCOPe have the most consistent domain boundary conditions, whereas CATH and SCOP2 both differ significantly."
pubmed.ncbi.nlm.nih.gov/34179613/

However that was before the AF2-explosion 😶

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

AFAIK PFAM was recently harmonized with ECOD
pubmed.ncbi.nlm.nih.gov/39565196/
pubmed.ncbi.nlm.nih.gov/39540428/
pubmed.ncbi.nlm.nih.gov/39197652/

And CATH has been massively expanded with the Encyclopedia of Domains (~7k putative novel folds)
pubmed.ncbi.nlm.nih.gov/39565206/

ECOD: integrating classifications of protein domains from experimental and predicted structures - PubMed

The evolutionary classification of protein domains (ECOD) classifies protein domains using a combination of sequence and structural data (http://prodata.swmed.edu/ecod). Here we present the culminatio...

pubmed.ncbi.nlm.nih.gov

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GAMA Miguel Angel @miangoar.bsky.social · Aug 27

Does anyone know of a recent comparison of the main structural classification schemes of proteins and guidance on when to choose one? Something like this but including ECOD and perhaps seq-based schemes like Pfam, SUPERFAMILY and CDD.

Img source (2020)
pubmed.ncbi.nlm.nih.gov/32302382/

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Reposted by GAMA Miguel Angel

Genome Biology and Evolution @genomebiolevol.bsky.social · Aug 26

In a new GBE Review, @cpuentelelievre.bsky.social @proteinmechanic.bsky.social & J. Douglas give an overview on protein structural phylogenetics, how to obtain evolutionary insights from structural data, and key applications and future directions.

🔗 doi.org/10.1093/gbe/evaf139

#genome #evolution

Puente-Lelievre et al. have systematically reviewed how protein structures can be used to trace evolutionary histories. This rapidly advancing field has not yet caught up with the burgeoning databases of high quality protein structure predictions provided by AlphaFold and other tools.

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