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

中文翻译：

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探索十亿范围内的化学空间：对接是 DNA 编码文库的计算替代方案吗？


DNA 编码库 (DEL) 的概念能够同时对数十亿种化合物进行实验筛选，从而前所未有地提高了化学空间的覆盖范围。然而，与此同时，超级计算机和大量超高通量虚拟筛选 (uHTVS) 工具的使用大幅增加，使得可以对数十亿成员的虚拟图书馆进行筛选。在这里，我们研究当前的、强力的或人工智能支持的 uHTVS 方法是否可以构成 DEL 筛选的计算替代方案。虽然人们很容易将 uHTVS 视为 DEL 筛选的计算模拟，但我们发现这两种方法的具体优点和局限性表明它们是互补的而不是竞争的。