6YKD

Human Pim-1 kinase in complex with an inhibitor identified by virtual screening

6YKD の概要

• エントリーDOI: 10.2210/pdb6ykd/pdb
• 分子名称: Serine/threonine-protein kinase pim-1, ~{N}-[3-[6-[(3~{R})-piperidin-3-yl]-2-pyridin-4-yl-pyrimidin-4-yl]oxyphenyl]ethanamide, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: kinase, cancer, transferase, atp-binding, virtual screening, apoptosis
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38265.27

構造登録者

Schneider, P.,Welin, M.,Svensson, B.,Walse, B.,Schneider, G. (登録日: 2020-04-06, 公開日: 2020-07-01, 最終更新日: 2024-11-06)

主引用文献

Schneider, P.,Welin, M.,Svensson, B.,Walse, B.,Schneider, G.
Virtual Screening and Design with Machine Intelligence Applied to Pim-1 Kinase Inhibitors.
Mol Inform, 39:e2000109-e2000109, 2020

PubMed 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.

PubMed: 33448694
DOI: 10.1002/minf.202000109

実験手法

X-RAY DIFFRACTION (1.86 Å)