Chemical space docking enables large-scale structure-based virtual screening to discover ROCK1 kinase inhibitors

Paul Beroza (), James J. Crawford, Oleg Ganichkin, Leo Gendelev, Seth F. Harris, Raphael Klein, Anh Miu, Stefan Steinbacher, Franca-Maria Klingler and Christian Lemmen
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Paul Beroza: Genentech
James J. Crawford: Genentech
Oleg Ganichkin: Proteros Biostructures GmbH
Leo Gendelev: Genentech
Seth F. Harris: Genentech
Raphael Klein: BioSolveIT GmbH
Anh Miu: Genentech
Stefan Steinbacher: Proteros Biostructures GmbH
Franca-Maria Klingler: BioSolveIT GmbH
Christian Lemmen: BioSolveIT GmbH

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: 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 Ki values

Date: 2022
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DOI: 10.1038/s41467-022-33981-8

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