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.