Closing the loop on #GenAI for #GPCR #SBDD www.nature.com/articles/s41... tinyurl.com/yeyhfr7j

Closing the loop on #GenAI for #GPCR #SBDD www.nature.com/articles/s41... tinyurl.com/yeyhfr7j

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.

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...

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...

#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...

@baoilleach.bsky.social on #Bluesky!

@baoilleach.bsky.social on #Bluesky!

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 🧪 🏺

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

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

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

Moving #CADD #AI for #GPCR #SBDD posts and discussions to #Bluesky ! bsky.app/profile/cdg-...

Comparative Ligandability Analysis and new Nomenclature Allosteric GPCR binding sites pubs.acs.org/doi/10.1021/... tinyurl.com/ybthux9c #GPCR #CADD #SBDD #ALLODD

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

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/...

#CASP16 results are online at the prediction center website - conference starting tomorrow evening. Have a safe trip - see you soon! predictioncenter.org/casp16/

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

1) Displace Energetically unfavorable water in lipophilic region with lipophilic ligand moiety

2) Stabilise Design favorable ligand-water-protein mediated interaction by introduction polar ligand moiety

3) Replace Polar ligand moiety mimicking energetically favorable water molecule

4) Leave alone a) Energetically favorable molecule b) Bulk water/accessible region / no need to expand ligand in this direction unless for eg solubilising groups

4-5 options/scenarios/sttategies how to deal with water in #SBDD #CADD #MedChem ? @darrylbmcconnell.bsky.social

Happy Thanksgiving to those celebrating! Here's some relevant chemistry for the day: www.compoundchem.com/2017/11/23/t... #ChemSky 🧪

4-5 options/scenarios/sttategies how to deal with water in #SBDD #CADD #MedChem ? @darrylbmcconnell.bsky.social

4) Leave alone a) Energetically favorable molecule b) Bulk water/accessible region / no need to expand ligand in this direction unless for eg solubilising groups

3) Replace Polar ligand moiety mimicking energetically favorable water molecule

2) Stabilise Design favorable ligand-water-protein mediated interaction by introduction polar ligand moiety

1) Displace Energetically unfavorable water in lipophilic region with lipophilic ligand moiety

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

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?

Just announced: 2025 Computer-Aided Drug Design (CADD) GRC program The topic: "Exploring the Synergy of Machine Learning and Physics-Based Computational Chemistry to Accelerate Drug Discovery" It is shaping up to be a seminal conference. Hope to see you there! www.grc.org/computer-aid...

We strongly suggest that academic publishers and other platforms that host research rapidly implement a Share to Bluesky button for their articles. Here's how: docs.bsky.app/docs/advance... #AcademicSky #HigherEd #Altmetrics

Moving #CADD #AI for #GPCR #SBDD posts and discussions to #Bluesky ! bsky.app/profile/cdg-...

Looking forward to interacting with GPCR experts at the GPCRs-Targeted Drug Discovery Summit - incl. Allosteric GPCR Drug Discovery workshop and presenting on Customising CADD for SBDD Targeting the Elusive Ligand & Water Induced GPCR Pocketome gpcrs-europe.com/whats-on/spe... #GPCR #CADD #SBDD

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

Comparative Ligandability Analysis and new Nomenclature Allosteric GPCR binding sites pubs.acs.org/doi/10.1021/... tinyurl.com/ybthux9c #GPCR #CADD #SBDD #ALLODD

Save the date: I'm happy to announce that the 2025 RDKit UGM will take place in Prague, Czechia from 10-12 September. The organizers are Martin Šícho and Daniel Svozil from the University of Chemistry and Technology in Prague. Registration details will follow early next year.

Interesting new paper on large scale small molecule model pre-training for property prediction by Recursion - pretraining in this domain isn’t necessarily as easy to get to work as in inages or language rdcu.be/dZWa9

Here's a Cheminformatics Starter pack! Let me know if you would like to be added! And more importantly, do encourage people to join the blue skies :D

I just joined Bluesky as well... let's rebuild the same nice community in the cheminformatics/comp chem/bioinformatics/drug discovery etc. areas that 'the other place' was in the good old days 😊! Looking forward to reconnecting with people here, Andreas