Journal of Computer-Aided Molecular Design

, Volume 21, Issue 6, pp 311–325 | Cite as

Structure and reaction based evaluation of synthetic accessibility

Original paper


De novo design systems provide powerful methods to suggest a set of novel structures with high estimated binding affinity. One deficiency of these methods is that some of the suggested structures could be synthesized only with great difficulty. We devised a scoring method that rapidly evaluates synthetic accessibility of structures based on structural complexity, similarity to available starting materials and assessment of strategic bonds where a structure can be decomposed to obtain simpler fragments. These individual components were combined to an overall score of synthetic accessibility by an additive scheme. The weights of the scoring function components were calculated by linear regression analysis based on accessibility scores derived from medicinal chemists. The calculated values for synthetic accessibility agree with the values proposed by chemists to an extent that compares well with how chemists agree with each other.


De novo design Reaction center Similarity search Synthetic accessibility 


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Krisztina Boda
    • 1
  • Thomas Seidel
    • 1
    • 2
  • Johann Gasteiger
    • 1
  1. 1.Computer-Chemie-CentrumUniversität Erlangen-NürnbergErlangenGermany
  2. 2.Institut für Angewandte SynthesechemieTechnische Universität WienViennaAustria

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