The Ledger
Every statement that passed quotation and attribution checks. Mix any filter with any other: certainty 1/5, debate potential 5/5, or both at once.
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Feinberg: Studies show AlphaFold structures provided no value for drug docking
“There is this, ah, a few papers that came out, one was in Cell, I think last year, which showed that for all of the claims about AlphaFold-solving drug discovery, people try to take AlphaFold-produced protein structures, use them for traditional docking, and f…”
Feinberg: The most innovative diffusion research is happening in 3D structure prediction
“What's kind of cool is right now for people that are interested in really core fundamental AI research, actually some of the most innovative diffusion research is happening in our field, is happening in three D structure prediction right now.”
Feinberg: High-throughput screening exhibits a shockingly low R-squared to actual synthesis
“The reality is that the translation of high throughput screens, whether it's Dell, DNA encoded libraries, or more traditional screens, the R-squared of those predictions to, like, the actual business of resynthesizing a molecule de novo and doing a Low through…”
Feinberg: Robotic lab automation trades off molecule novelty and quality for speed
“The kinds of chemistries that today can be automated are fairly constrained. And so your ability to search chemical space broadly for those really top top Pareto optimal compounds is, is actually very limited. So the benefits you get in speed have a very harsh…”
Feinberg: Chipmakers will invest in life sciences as LLM alpha shrinks
“I do think that chip makers, including Nvidia, are going to want to get a lot more invested in life sciences because it will always be high in demand. And The amount of alpha left in pure LLM space is just getting a little questionable.”
Feinberg: Drug discovery and design is AI's highest-leverage application in healthcare
“Our contention is that the highest leverage application of artificial intelligence
Is the drug discovery and drug design process.”
Feinberg: Gemini is obviously worse at coding despite benchmark wins
“So Gemini does pretty well on Sweebench. Sometimes Gemini publishes models that win on some of those software benchmarks. Raise your hand if you're using Gemini to write code right now instead of, you know, the obvious other name competitors. No one. Like, why…”
Feinberg: Biological target validation is orthogonal to druggability
“Known biology is orthogonal to the ease with which one can drug that target. Sometimes, unfortunately, it seems they anti-correlate in that often it seems that the most appealing targets from a validation perspective seem to be really hard to drug.”
Feinberg: Genesis is developing autonomous drug discovery agent platform 'Sapphire'
“We're working on an agentic platform for 24 seven drug discovery. If you can imagine just fleets of hundreds of med chemists and CAD scientists Working nights and weekends all the time for your drug targets. The code name for that gem is Sapphire.”
Feinberg: Potent ligands have well-defined 3D positions down to 0.5 angstroms
“The reality is that for a highly potent ligand, Almost certainly, there is a large portion of that molecule with a very well-defined three-D position, down to even half angstrom.”
Feinberg: Small molecules make up 65% of FDA-approved drugs
“Small molecules are still 65% of FDA approved drugs, so we're talking about the biggest part of the pie.”
Feinberg: Drug candidates must pass over 30 distinct assay properties
“I would say there's over 30 or so assays, each of which you could imagine if you're a neural net person, like a multitask neural network or multi-head, it's got to predict over 30, you know, three dozen-ish properties, each of which, if it's in the wrong range…”
Feinberg: GANs failed for protein modeling due to mode collapse before diffusion emerged
“For all the same reasons that those models were really tricky to train for images. Mode collapse was the most famous sort of problem. They didn't work very well for proteins or protein ligand systems. And we sort of had to wait for the right primitive to get c…”
Feinberg: Solving experimental 3D protein structures takes months and tens of thousands
“Like you might as well solve the three D crystal structure or cryo-EM structure is what you're saying, which can cost tens of thousands of dollars. It can be months or years. Right. Entire PhD theses, postdocs can sometimes work literally 24 seven trying to so…”