Exploring Chemical\nSpaces in the Billion Range: Is\nDocking a Computational Alternative to DNA-Encoded Libraries?

The concept of DNA-encoded libraries (DELs) enables the\nexperimental\nscreening of billions of compounds simultaneously, offering an unprecedented\nboost in the coverage of chemical space. In parallel, however, dramatically\nincreased access to supercomputers and a number of ultrahigh throughput\nvirtual screening (uHTVS) tools have made screening of billion-membered\nvirtual libraries available. Here, we investigate whether current,\nbrute-force, or AI-enabled uHTVS approaches might constitute a computational\nalternative to DEL screening. While it is tempting to look at uHTVS\nas a computational analogue of DEL screening, we found specific advantages\nand limitations of both methodologies that suggest them being complementary\nrather than competitive.