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Back to 🔬 Lab-in-the-Loop at Compute Speed — Ian Quigley, Leash Bio, with Ian Quigley & RJ Honicky.

What Small-molecule Cleanup Does Ian Quigley Want?

Ian Quigley wants small-molecule cleanup that can run at massive scale. The gizmos that purify well, including HPLC, are not highly parallel.

Making a molecule means putting material in a pot and heating it, or using some other conditions. The output lands at an efficiency that might be great or might be poor. Either way, and especially when the result is poor, another set of gizmos has to clean it up. People use HPLC and similar tricks, and none of the really good ones are super parallelizable. His lab runs many molecules through a funky assay already described as giving people lots of trauma. Large numbers of molecules that are clean, purified, and easy to work with could then go into a different assay, and the new measurements could orthogonally validate the ones already collected.

Asked what he would remove by fiat if it has not already been removed, he picks that gap: purification good enough to trust and parallel enough for huge numbers of molecules.

Transcript

🔬 Lab-in-the-Loop at Compute Speed — Ian Quigley, Leash Bio ·

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  5. How Reproducible Are Leash Bio Binding Screens?Ian Quigley says about 90% of chemicals that are easy in their hands still work after they are made off DNA and run in functional assays, and about 50% of the…
  6. What Is a Small Molecule Drug?Ian Quigley calls a small molecule a tiny chemical that can sit in a pill, go inside a cell, and affect how a protein behaves.
  7. Did Anyone Beat Chance on the Hardest Leash Bio Binding Test?Ian Quigley says that on the hardest split of Leash Bio's public binding contest, nobody did better than chance, and three of the top five entries were a…
  8. Why Do Binding Models Learn the Chemist Instead of the Chemistry?Ian Quigley says a model can predict ChEMBL activity from who probably made a molecule about as well as it can from the chemical formula, so it is learning…
  9. Did Hermes Match Boltz on Binding Prediction?Ian Quigley says Hermes did about as well as Boltz, then the state of the art structural model, on public data sets for binding prediction.
  10. What Is a Magic Methyl in Drug Design?Ian Quigley says a magic methyl is the medicinal-chemistry story that one tiny thorn on a molecule can make it work or make it fail, and he calls that story…
  11. Why Do Structure Models Put a Drug Back Into a Filled Pocket?Ian Quigley says current co-folding models still place a small molecule where a pocket used to be after that pocket has been filled in, removed, or broken.
  12. How Does Breaking a Protein Pocket Prove Binding?Ian Quigley says breaking one pocket with a mutation shows which chemicals were binding there.
  13. Why Does the Hermes Binding Model Nickname a Protein?Ian Quigley says the Hermes binding model nicknames a protein by memorizing a short variable stretch of amino acids, instead of looking at the binding pocket…
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  16. How Many Proteins Has Leash Bio Screened?Ian Quigley says Leash Bio has developed and screened about 2,000 different protein constructs and about 5,000 screens in the history of the company, each…
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