Alexey Ereshchenko, Sergei Evteev, Alexander Malyshev, Denis Adjugim, Fedor Sizov, Anna Pastukhova, Victor Terentiev, Petr Shegai, Andrey Kaprin, Yan Ivanenkov
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Enhancing accuracy of virtual kinase profiling via application of graph neural network to 3D pharmacophore ensembles
Kinase profiling is an essential step in both hit identification and selectivity evaluation. Since in vitro testing of large chemical libraries is costly and time-consuming, a computational approach can be applied to narrow down the reasonable chemical space. In this work, we collected data from several sources and prepared a curated, comprehensive database for training machine learning (ML) models to predict selectivity towards 75 kinases. We demonstrated the usefulness of this database by preparing several ML models with various molecular representations and model architectures. Among these, a graph neural network-based model enhanced by utilizing 3D pharmacophore ensembles showed the best performance. Finally, the developed model was applied to a library of in-stock compounds to facilitate kinase-focused drug discovery.
期刊介绍：
The Journal of Computer-Aided Molecular Design provides a form for disseminating information on both the theory and the application of computer-based methods in the analysis and design of molecules. The scope of the journal encompasses papers which report new and original research and applications in the following areas:
- theoretical chemistry;
- computational chemistry;
- computer and molecular graphics;
- molecular modeling;
- protein engineering;
- drug design;
- expert systems;
- general structure-property relationships;
- molecular dynamics;
- chemical database development and usage.
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