Structure and reaction based evaluation of synthetic accessibility |
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Authors: | Krisztina Boda Thomas Seidel Johann Gasteiger |
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Institution: | 1.Computer-Chemie-Centrum,Universit?t Erlangen-Nürnberg,Erlangen,Germany;2.Institut für Angewandte Synthesechemie,Technische Universit?t Wien,Vienna,Austria |
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Abstract: | 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. |
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Keywords: | De novo design Reaction center Similarity search Synthetic accessibility |
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