Stochastic Voyages into Uncharted Chemical Space Produce a Representative Library of All Possible Drug-Like Compounds

The “small molecule universe” (SMU), the set of all synthetically feasible organic molecules of 500 Da molecular weight or less, is estimated to contain over 1060 structures, making exhaustive searches for structures of interest impractical. Here, we describe the construction of a “representative universal library” spanning the SMU that samples the full extent of feasible small molecule chemistries. This library was generated using the newly developed Algorithm for Chemical Space Exploration with Stochastic Search (ACSESS). ACSESS makes two important contributions to chemical space exploration: it allows the systematic search of the unexplored regions of the small molecule universe, and it facilitates the mining of chemical libraries that do not yet exist, providing a near-infinite source of diverse novel compounds.

小分子宇宙（small molecule universe, SMU）指所有分子量不超过500道尔顿（Da）的可合成有机分子集合，据估计其包含超过10⁶⁰种结构，这使得针对目标结构的穷尽式搜索变得极不切实际。本文介绍了一种覆盖该小分子宇宙的代表性通用文库的构建方法，该文库可对全部可行的小分子化学空间进行完整采样。该文库基于新开发的随机搜索化学空间探索算法（Algorithm for Chemical Space Exploration with Stochastic Search, ACSESS）生成。ACSESS为化学空间探索领域带来两项重要贡献：其一，它可实现对小分子宇宙中未被探索区域的系统性搜索；其二，它能够助力挖掘尚未存在的化学文库，为多样化的新型化合物提供近乎无限的来源。