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Virtual Screening and Design with Machine Intelligence Applied to Pim-1 Kinase Inhibitors.

ABSTRACT: Ligand-based virtual screening of large compound collections, combined with fast bioactivity determination, facilitate the discovery of bioactive molecules with desired properties. Here, chemical similarity based machine learning and label-free differential scanning fluorimetry were used to rapidly identify new ligands of the anticancer target Pim-1 kinase. The three-dimensional crystal structure complex of human Pim-1 with ligand bound revealed an ATP-competitive binding mode. Generative de novo design with a recurrent neural network additionally suggested innovative molecular scaffolds. Results corroborate the validity of the chemical similarity principle for rapid ligand prototyping, suggesting the complementarity of similarity-based and generative computational approaches.

SUBMITTER: Schneider P

PROVIDER: S-EPMC7539333 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Virtual Screening and Design with Machine Intelligence Applied to Pim-1 Kinase Inhibitors.

Schneider Petra P Welin Martin M Svensson Bo B Walse Björn B Schneider Gisbert G

Molecular informatics 20200709 9

Ligand-based virtual screening of large compound collections, combined with fast bioactivity determination, facilitate the discovery of bioactive molecules with desired properties. Here, chemical similarity based machine learning and label-free differential scanning fluorimetry were used to rapidly identify new ligands of the anticancer target Pim-1 kinase. The three-dimensional crystal structure complex of human Pim-1 with ligand bound revealed an ATP-competitive binding mode. Generative de nov ...[more]

PMID: 33448694

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