How Many Molecules Can One DNA-encoded Library Hold?

Ian Quigley says the largest DNA-encoded library produced holds 40 trillion molecules, while the biggest one-chemical-at-a-time collections sit in the low single-digit millions.

The slow path puts different chemicals in different tubes and dunks the protein in one tube at a time. A DNA-encoded library puts many chemicals in one tube, each carrying a small DNA barcode. The protein goes in like a fishhook, the binders come back out, and the barcodes are sequenced, which skips the overhead of huge plate runs. He says there are problems when a library gets to 40 trillion. The mixtures are combinatorial. Thousands or tens of thousands of building blocks, squared or cubed depending on the design, become many millions of molecules. That locks the chemistry to those blocks. It also helps a model, because the combinations match except for one or two changes, which shows which part of the small molecule drives binding.