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Gimadiev, T.* ; Madzhidov, T.* ; Tetko, I.V. ; Nugmanov, R.* ; Casciuc, I.* ; Klimchuk, O.* ; Bodrov, A.* ; Polishchuk, P.* ; Antipin, I.* ; Varnek, A.*

Bimolecular nucleophilic substitution reactions: Predictive models for rate constants and Molecular Reaction Pairs analysis.

Mol. Inform. 38:1800104 (2019)
Postprint Research data DOI PMC
Open Access Green
Here, we report the data visualization, analysis and modeling for a large set of 4830 S(N)2 reactions the rate constant of which (logk) was measured at different experimental conditions (solvent, temperature). The reactions were encoded by one single molecular graph - Condensed Graph of Reactions, which allowed us to use conventional chemoinformatics techniques developed for individual molecules. Thus, Matched Reaction Pairs approach was suggested and used for the analyses of substituents effects on the substrates and nucleophiles reactivity. The data were visualized with the help of the Generative Topographic Mapping approach. Consensus Support Vector Regression (SVR) model for the rate constant was prepared. Unbiased estimation of the model's performance was made in cross-validation on reactions measured on unique structural transformations. The model's performance in cross-validation (RMSE=0.61 logk units) and on the external test set (RMSE=0.80) is close to the noise in data. Performances of the local models obtained for selected subsets of reactions proceeding in particular solvents or with particular type of nucleophiles were similar to that of the model built on the entire set. Finally, four different definitions of model's applicability domains for reactions were examined.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Bimolecular Nucleophilic Substitution Reactions ; Condensed Graph Of Reaction ; Matched Reaction Pairs ; Support Vector Regression ; Generative Topographic Mapping ; Models Applicability Domain; Solvatochromic Comparison Method; Applicability Domain; S(n)2 Reactions; Scale; Graph; Representation
ISSN (print) / ISBN 1868-1743
e-ISSN 1868-1751
Journal Molecular Informatics
Quellenangaben Volume: 38, Issue: 4, Pages: , Article Number: 1800104 Supplement: ,
Publisher Wiley
Publishing Place Weinheim
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)