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Reposted by Chris de Graaf

Chris de Graaf @cdg-gpcr.bsky.social · Jul 2

Closing the loop on #GenAI for #GPCR #SBDD

www.nature.com/articles/s41...

tinyurl.com/yeyhfr7j

Identification of nanomolar adenosine A2A receptor ligands using reinforcement learning and structure-based drug design - Nature Communications

Here the authors combine a deep generative model with structure-based drug design and prospectively validate functionally active, nanomolar, A2A adenosine receptor ligands and solve their crystal stru...

www.nature.com

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Chris de Graaf @cdg-gpcr.bsky.social · Jul 2

Closing the loop on #GenAI for #GPCR #SBDD

www.nature.com/articles/s41...

tinyurl.com/yeyhfr7j

Identification of nanomolar adenosine A2A receptor ligands using reinforcement learning and structure-based drug design - Nature Communications

Here the authors combine a deep generative model with structure-based drug design and prospectively validate functionally active, nanomolar, A2A adenosine receptor ligands and solve their crystal stru...

www.nature.com

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Reposted by Chris de Graaf

Derek Lowe @dereklowe.bsky.social · Feb 12

Biopharma companies and CEOs are keeping their heads down at their own peril. They should speak up about what’s happening to the NIH and other science agencies before it’s too late.

Silence gives consent. And no one should consent to this.

Stand Up And Be Counted

www.science.org

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Reposted by Chris de Graaf

Diego del Alamo @delalamo.xyz · Jan 19

Protein backbone diffusion models consistently undersample catalytically important motifs, and oversample idealized helices, raising questions about the appropriateness of these methods in designing starting points for enzyme design & evolution. From www.biorxiv.org/content/10.1...

Protein structure embeddings reveal undersampled and de novo structure space. (B) First two principal components of mean-pooled ESM3 embeddings colored by helix content determined by DSSP. The indicated dashed guide lines denote visual boundaries of native structure space not sampled (Undersampled) and novel regions of protein structure for this space only observed in samples but not in native structures (De novo). (C) Rasterized visualization of panel B with 16 equally spaced grid squares in each principal component axis. A representative structure from each grid was chosen at random. Empty grid squares indicate the absence of any structure in the enclosed region. De novo alpha helices are shaded along the lower-right diagonal and the structures from CATH which do not have corresponding structures in the samples are shaded along the left and top rims. The structures are displayed in CATH raster plot are given in the Supplementary Information.

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Reposted by Chris de Graaf

Gerard JP van Westen @gjpvwesten.bsky.social · Jan 17

If you are interested in #AI and #DrugDiscovery, attend the upcoming ICCS June 1st - Jun 5th in Noordwijkerhout!

Last call for papers. Please repost!

Registration and abstracts (deadline 14 Feb): iccs-nl.org/general-info...

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Chris de Graaf @cdg-gpcr.bsky.social · Jan 10

Many thanks @gati.bsky.social!

Chris de Graaf @cdg-gpcr.bsky.social · Jan 10

#StructuralBiology insights into #Genetic #GPCR variations identified in the UK 100,000 Genomes Project with differentiating effects on peptide (affected) vs. small molecule agonists (not affected) #pharmacology

www.nature.com/articles/s41...

Structural and functional determination of peptide versus small molecule ligand binding at the apelin receptor - Nature Communications

This study explores apelin receptor’s role in cardiovascular function, identifying residues critical for binding through genetic variants, AlphaFold2 modelling and base editing in cardiomyocytes. Co-c...

www.nature.com

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Reposted by Chris de Graaf

Chris de Graaf @cdg-gpcr.bsky.social · Dec 15

@baoilleach.bsky.social on #Bluesky!

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Chris de Graaf @cdg-gpcr.bsky.social · Dec 15

@baoilleach.bsky.social on #Bluesky!

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Reposted by Chris de Graaf

Nature Portfolio @natureportfolio.nature.com · Dec 13

Analysis of the oldest-known genomes from early modern humans in Europe, who lived around 45,000 years ago, helps to provide a more precise date for when Neanderthals and modern humans mixed, according to research published in Nature. https://go.nature.com/3ZR8Kh1 🧪 🏺

This is figure 1, which shows the geographical distribution of modern human specimens older than 40 ky that produced genome wide data

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Reposted by Chris de Graaf

Pat Walters @wpwalters.bsky.social · Dec 12

ChEMBL 35 is out. Happy Holidays!
chembl.blogspot.com/2024/12/here...

Here's a nice Christmas gift - ChEMBL 35 is out!

Use your well-deserved Christmas holidays to spend time with your loved ones and explore the new release of ChEMBL 35! This fresh...

chembl.blogspot.com

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Chris de Graaf @cdg-gpcr.bsky.social · Dec 9

Reply by Jain and colleagues on the response of Corso and colleagues:.
More response to the response (DiffDock/DiffDock-L)
www.linkedin.com/pulse/more-r...

More response to the response (DiffDock/DiffDock-L)

To amplify on what Pat Walters said (quotes from Gabriel Corso's post in italics): It only took a few days (in August 2023) for Ann Cleves, Pat, and me to figure out that the original DiffDock work ha...

www.linkedin.com

Reposted by Chris de Graaf

Marwin Segler @marwinsegler.bsky.social · Dec 9

new preprint on chemical synthesis ML models

- showing how to combine multiple models in a principled way
- modern Transformers + GNN to featurize chemical reaction:
- new insights in where the models shine
+ bonus: find the quirky named reaction!

Feedback welcome!

arxiv.org/abs/2412.05269

Chimera: Accurate retrosynthesis prediction by ensembling models with diverse inductive biases

Planning and conducting chemical syntheses remains a major bottleneck in the discovery of functional small molecules, and prevents fully leveraging generative AI for molecular inverse design. While ea...

arxiv.org

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Reposted by Chris de Graaf

Alt National Park Service @altnps.bsky.social · Dec 7

We keep getting messages saying climate change is a hoax and the world is flat. Is it 2024?!

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Chris de Graaf @cdg-gpcr.bsky.social · Dec 1

Of: Alles voor zoete koek slikken

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Reposted by Chris de Graaf

John P. Overington @jpoverington.bsky.social · Nov 27

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Reposted by Chris de Graaf

Chris de Graaf @cdg-gpcr.bsky.social · Nov 23

Moving #CADD #AI for #GPCR #SBDD posts and discussions to #Bluesky !

bsky.app/profile/cdg-...

Chris de Graaf @cdg-gpcr.bsky.social · Nov 23

Closing the CADD AI SBDD loop - From GPCR structures to RNN de novo drug design and back again!

chemrxiv.org/engage/chemr...

#GPCR #AI #RNN #CADD #SBDD

Modern hit-finding with structure-guided de novo design: identification of novel nanomolar adenosine A2A receptor ligands using reinforcement learning

Generative chemical language models have demonstrated success in learning language-based molecular representations for de novo drug design. Here, we integrate structure-based drug design (SBDD) princi...

chemrxiv.org

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Reposted by Chris de Graaf

Chris de Graaf @cdg-gpcr.bsky.social · Nov 23

Comparative Ligandability Analysis and new Nomenclature Allosteric GPCR binding sites

pubs.acs.org/doi/10.1021/...

tinyurl.com/ybthux9c

#GPCR #CADD #SBDD #ALLODD

Comparative Study of Allosteric GPCR Binding Sites and Their Ligandability Potential

The steadily growing number of experimental G-protein-coupled receptor (GPCR) structures has revealed diverse locations of allosteric modulation, and yet few drugs target them. This gap highlights the...

pubs.acs.org

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Reposted by Chris de Graaf

Chris de Graaf @cdg-gpcr.bsky.social · Nov 23

Closing the CADD AI SBDD loop - From GPCR structures to RNN de novo drug design and back again!

chemrxiv.org/engage/chemr...

#GPCR #AI #RNN #CADD #SBDD

Modern hit-finding with structure-guided de novo design: identification of novel nanomolar adenosine A2A receptor ligands using reinforcement learning

Generative chemical language models have demonstrated success in learning language-based molecular representations for de novo drug design. Here, we integrate structure-based drug design (SBDD) princi...

chemrxiv.org

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Reposted by Chris de Graaf

Polaris @polarishub.io · Nov 25

The first paper from the Small Molecule Steering Committee at Polaris introduced practical guidelines for method comparison in ML-driven drug discovery.

We'll be discussing this live on Dec 5th from 11 - 12 PM ET.

Join the convo: portal.valencelabs.com/events/post/...

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Chris de Graaf @cdg-gpcr.bsky.social · Dec 1

Bijvoorbeeld: Koekje van eigen deeg

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Chris de Graaf @cdg-gpcr.bsky.social · Dec 1

🙋‍♂️👨‍💻

Reposted by Chris de Graaf

Torsten Schwede @torstenschwede.bsky.social · Dec 1

#CASP16 results are online at the prediction center website - conference starting tomorrow evening.

Have a safe trip - see you soon!

predictioncenter.org/casp16/

Home - CASP16

predictioncenter.org

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Reposted by Chris de Graaf

Chris de Graaf @cdg-gpcr.bsky.social · Nov 28

More generally (not for HIV protease case specifically) I would propose to consider 4-5 options:

Darryl B McConnell @darrylbmcconnell.bsky.social · Nov 28

What to do with waters in drug discovery is one of the most important decisions that drug designers need to make. What would you do with the FLAP water on HIV protease? Address or Replace?

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