7S25
ROCK1 IN COMPLEX WITH LIGAND G4998
Summary for 7S25
| Entry DOI | 10.2210/pdb7s25/pdb |
| Descriptor | Rho-associated protein kinase 1, CHLORIDE ION, 2-[3-(methoxymethyl)phenyl]-N-[4-(1H-pyrazol-4-yl)phenyl]acetamide, ... (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 | 184474.17 |
| Authors | Ganichkin, O.,Harris, S.F.,Steinbacher, S. (deposition date: 2021-09-03, release date: 2022-10-05, Last modification date: 2024-04-03) |
| 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 Cited by 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: 36307407DOI: 10.1038/s41467-022-33981-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.337 Å) |
Structure validation
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