7S26

ROCK1 IN COMPLEX WITH LIGAND G5018

Summary for 7S26

• Entry DOI: 10.2210/pdb7s26/pdb
• Descriptor: 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)
• Functional Keywords: rho kinase, proteros biostructures gmbh, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 185552.20

Authors

Ganichkin, O.,Harris, S.F.,Steinbacher, S. (deposition date: 2021-09-03, release date: 2022-10-05, Last modification date: 2024-05-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.744 Å)