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Structure–reactivity modeling using mixture-based representation of chemical reactions

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Abstract

We describe a novel approach of reaction representation as a combination of two mixtures: a mixture of reactants and a mixture of products. In turn, each mixture can be encoded using an earlier reported approach involving simplex descriptors (SiRMS). The feature vector representing these two mixtures results from either concatenated product and reactant descriptors or the difference between descriptors of products and reactants. This reaction representation doesn’t need an explicit labeling of a reaction center. The rigorous “product-out” cross-validation (CV) strategy has been suggested. Unlike the naïve “reaction-out” CV approach based on a random selection of items, the proposed one provides with more realistic estimation of prediction accuracy for reactions resulting in novel products. The new methodology has been applied to model rate constants of E2 reactions. It has been demonstrated that the use of the fragment control domain applicability approach significantly increases prediction accuracy of the models. The models obtained with new “mixture” approach performed better than those required either explicit (Condensed Graph of Reaction) or implicit (reaction fingerprints) reaction center labeling.

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Acknowledgements

This work was supported by Russian Science Foundation, Grant No. 14-43-00024.

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Authors and Affiliations

  1. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

    Pavel Polishchuk

  2. A.V. Bogatsky Physico-Chemical Institute of National Academy of Sciences of Ukraine, Odessa, Ukraine

    Pavel Polishchuk

  3. A.M. Butlerov Institute of Chemistry, Kazan Federal University, Kazan, Russia

    Pavel Polishchuk, Timur Madzhidov, Timur Gimadiev, Andrey Bodrov, Ramil Nugmanov & Alexandre Varnek

  4. Department of General and Organic Chemistry, Kazan State Medical University, Kazan, Russia

    Andrey Bodrov

  5. Laboratory of Chemoinformatics, University of Strasbourg, Strasbourg, France

    Timur Gimadiev & Alexandre Varnek

Authors
  1. Pavel Polishchuk
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  2. Timur Madzhidov
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  3. Timur Gimadiev
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  4. Andrey Bodrov
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  5. Ramil Nugmanov
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  6. Alexandre Varnek
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Correspondence to Pavel Polishchuk, Timur Madzhidov or Alexandre Varnek.

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Polishchuk, P., Madzhidov, T., Gimadiev, T. et al. Structure–reactivity modeling using mixture-based representation of chemical reactions. J Comput Aided Mol Des 31, 829–839 (2017). https://doi.org/10.1007/s10822-017-0044-3

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  • DOI: https://doi.org/10.1007/s10822-017-0044-3

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