7S26

ROCK1 IN COMPLEX WITH LIGAND G5018

7S26 の概要

• エントリーDOI: 10.2210/pdb7s26/pdb
• 分子名称: Rho-associated protein kinase 1, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, 2-[methyl(phenyl)amino]-1-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-3,6-dihydropyridin-1(2H)-yl]ethan-1-one, ... (4 entities in total)
• 機能のキーワード: rho kinase, proteros biostructures gmbh, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 185552.20

構造登録者

Ganichkin, O.,Harris, S.F.,Steinbacher, S. (登録日: 2021-09-03, 公開日: 2022-10-05, 最終更新日: 2024-05-22)

主引用文献

Beroza, P.,Crawford, J.J.,Ganichkin, O.,Gendelev, L.,Harris, S.F.,Klein, R.,Miu, A.,Steinbacher, S.,Klingler, F.M.,Lemmen, C.
Chemical space docking enables large-scale structure-based virtual screening to discover ROCK1 kinase inhibitors.
Nat Commun, 13:6447-6447, 2022

PubMed Abstract: With the ever-increasing number of synthesis-on-demand compounds for drug lead discovery, there is a great need for efficient search technologies. We present the successful application of a virtual screening method that combines two advances: (1) it avoids full library enumeration (2) products are evaluated by molecular docking, leveraging protein structural information. Crucially, these advances enable a structure-based technique that can efficiently explore libraries with billions of molecules and beyond. We apply this method to identify inhibitors of ROCK1 from almost one billion commercially available compounds. Out of 69 purchased compounds, 27 (39%) have K values < 10 µM. X-ray structures of two leads confirm their docked poses. This approach to docking scales roughly with the number of reagents that span a chemical space and is therefore multiple orders of magnitude faster than traditional docking.

PubMed: 36307407
DOI: 10.1038/s41467-022-33981-8

実験手法

X-RAY DIFFRACTION (2.744 Å)