Article open access publication

Finding the K best synthesis plans

Journal of Cheminformatics, Springer Nature, ISSN 1758-2946

Volume 10, 1, 2018

DOI:10.1186/s13321-018-0273-z, Dimensions: pub.1103148932, PMC: PMC5887019, PMID: 29623440,

Authors

Kianian, Rojin (1) (3) (4)
Stadler, Peter F. * (2) (3) (4) (5) (6) (7)

* Corresponding author

Affiliations

Organisations

  1. (1) University of Southern Denmark, grid.10825.3e, SDU
  2. (2) University of Vienna, grid.10420.37
  3. (3) Bioinformatics Group, Department of Computer Science, Interdisciplinary Center for Bioinformatics, Härtelstraße 16-18, 04107, Leipzig, Germany
  4. (4) Max Planck Institute for Mathematics in the Sciences, grid.419532.8
  5. (5) Fraunhofer Institute for Cell Therapy and Immunology, grid.418008.5
  6. (6) Santa Fe Institute, grid.209665.e
  7. (7) University of Copenhagen, grid.5254.6, KU

Description

In synthesis planning, the goal is to synthesize a target molecule from available starting materials, possibly optimizing costs such as price or environmental impact of the process. Current algorithmic approaches to synthesis planning are usually based on selecting a bond set and finding a single good plan among those induced by it. We demonstrate that synthesis planning can be phrased as a combinatorial optimization problem on hypergraphs by modeling individual synthesis plans as directed hyperpaths embedded in a hypergraph of reactions (HoR) representing the chemistry of interest. As a consequence, a polynomial time algorithm to find the K shortest hyperpaths can be used to compute the K best synthesis plans for a given target molecule. Having K good plans to choose from has many benefits: it makes the synthesis planning process much more robust when in later stages adding further chemical detail, it allows one to combine several notions of cost, and it provides a way to deal with imprecise yield estimates. A bond set gives rise to a HoR in a natural way. However, our modeling is not restricted to bond set based approaches-any set of known reactions and starting materials can be used to define a HoR. We also discuss classical quality measures for synthesis plans, such as overall yield and convergency, and demonstrate that convergency has a built-in inconsistency which could render its use in synthesis planning questionable. Decalin is used as an illustrative example of the use and implications of our results.

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Times Cited: 2

Field Citation Ratio (FCR): 0.64

Relative Citation ratio (RCR): 0.33

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