Strategy To Discover Diverse Optimal Molecules in the Small Molecule Universe

The small molecule universe (SMU) is defined as a set of over 1060 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 app...

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Bibliographic Details
Published in:Journal of chemical information and modeling 2015-03, Vol.55 (3), p.529-537
Main Authors: Rupakheti, Chetan, Virshup, Aaron, Yang, Weitao, Beratan, David N
Format: Article
Language:English
Subjects:
Algorithms
Chemistry
Enumeration
Landscapes
Libraries
Models, Chemical
Molecular Weight
Molecules
Optimization
Physical properties
Small Molecule Libraries - chemistry
Stochastic models
Stochastic Processes
Strategy
Universe
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Summary:The small molecule universe (SMU) is defined as a set of over 1060 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 × 105 molecules.
ISSN:1549-9596
1549-960X
DOI:10.1021/ci500749q