title: Strategy to discover diverse optimal molecules in the small molecule universe.
abstract: The small molecule universe (SMU) is defined as a set of over 10(60) synthetically feasible organic molecules with molecular weight less than ∼500 Da. Exhaustive enumerations and evaluation of all SMU molecules for the purpose of discovering favorable structures is impossible. We take a stochastic approach and extend the ACSESS framework ( Virshup et al. J. Am. Chem. Soc. 2013 , 135 , 7296 - 7303 ) to develop diversity oriented molecular libraries that can generate a set of compounds that is representative of the small molecule universe and that also biases the library toward favorable physical property values. We show that the approach is efficient compared to exhaustive enumeration and to existing evolutionary algorithms for generating such libraries by testing in the NKp fitness landscape model and in the fully enumerated GDB-9 chemical universe containing 3 × 10(5) molecules.
authors.affiliation: †Program in Computational Biology and Bioinformatics, ‡Department of Chemistry, §Department of Physics, and ∥Department of Biochemistry, Duke University, Durham, North Carolina 27708, United States.
authors.forename: Chetan
authors.initials: C
authors.lastname: Rupakheti
authors.affiliation: †Program in Computational Biology and Bioinformatics, ‡Department of Chemistry, §Department of Physics, and ∥Department of Biochemistry, Duke University, Durham, North Carolina 27708, United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: Virshup
authors.affiliation: †Program in Computational Biology and Bioinformatics, ‡Department of Chemistry, §Department of Physics, and ∥Department of Biochemistry, Duke University, Durham, North Carolina 27708, United States.
authors.forename: Weitao
authors.initials: W
authors.lastname: Yang
authors.affiliation: †Program in Computational Biology and Bioinformatics, ‡Department of Chemistry, §Department of Physics, and ∥Department of Biochemistry, Duke University, Durham, North Carolina 27708, United States.
authors.forename: David N
authors.initials: DN
authors.lastname: Beratan
mesh_terms: D000465:Algorithms; D008956:Models, Chemical; D008970:Molecular Weight; D054852:Small Molecule Libraries / Q000737:chemistry*; D013269:Stochastic Processes
chemical_list: D054852:Small Molecule Libraries