CACHE (Critical Assessment of Computational Hit-finding Experiments): A public-private partnership benchmarking initiative to enable the development of computational methods for hit-finding.

Autor: Ackloo S; Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada., Al-Awar R; Ontario Institute for Cancer Research, Toronto, Ontario, Canada.; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada., Amaro RE; Department of Chemistry and Biochemistry, UC San Diego, La Jolla, CA, USA.; Drug Design Data Resource, University of California, San Diego, La Jolla, CA, USA., Arrowsmith CH; Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada., Azevedo H; Aché Laboratórios Farmacêuticos, Guarulhos, São Paulo, Brazil., Batey RA; Department of Chemistry, University of Toronto, Toronto, Ontario, Canada., Bengio Y; Mila, University of Montreal, Québec, Canada., Betz UAK; Merck Healthcare KGaA, Darmstadt, Germany., Bologa CG; Department of Internal Medicine, University of New Mexico School of Medicine, University of New Mexico Albuquerque, Albuquerque, NM, USA., Chodera JD; Computational and Systems Biology Program Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Cornell WD; Healthcare & Life Sciences Research, IBM TJ Watson Research Center, New York, USA., Dunham I; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK.; Open Targets, Wellcome Genome Campus, Hinxton, UK., Ecker GF; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria., Edfeldt K; Structural Genomics Consortium, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden., Edwards AM; Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada., Gilson MK; Drug Design Data Resource, University of California, San Diego, La Jolla, CA, USA.; Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, CA, USA., Gordijo CR; Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada., Hessler G; Sanofi-Aventis Deutschland GmbH, R&D, Integrated Drug Discovery, Frankfurt am Main, Germany., Hillisch A; Bayer AG, Pharmaceuticals, Research and Development, Wuppertal, Germany., Hogner A; Medicinal Chemistry, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Irwin JJ; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA., Jansen JM; Novartis Institutes for BioMedical Research, Emeryville, CA, USA., Kuhn D; Merck Healthcare KGaA, Computational Chemistry & Biologics, Darmstadt, Germany., Leach AR; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK.; Open Targets, Wellcome Genome Campus, Hinxton, UK., Lee AA; PostEra Inc, San Franciso, CA, USA.; Department of Physics, University of Cambridge, Cambridge, UK., Lessel U; Boehringer Ingelheim Pharma GmbH & Co. KG, Medicinal Chemistry, Biberach an der Riss, Germany., Morgan MR; Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada., Moult J; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA., Muegge I; Alkermes, Inc., Waltham, MA, USA., Oprea TI; Department of Internal Medicine, University of New Mexico School of Medicine, University of New Mexico Albuquerque, Albuquerque, NM, USA.; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA., Perry BG; Drugs for Neglected Diseases initiative, Geneva, Switzerland., Riley P; Relay Therapeutics, Boston, MA, USA., Rousseaux SAL; Department of Chemistry, University of Toronto, Toronto, Ontario, Canada., Saikatendu KS; Global Research Externalization, Takeda California, Inc., San Diego, CA, USA., Santhakumar V; Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada., Schapira M; Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada., Scholten C; Bayer AG, Pharmaceuticals, Open Innovation - Public Private Partnerships, Berlin, Germany., Todd MH; School of Pharmacy, University College London, London, UK., Vedadi M; Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada., Volkamer A; In Silico Toxicology and Structural Bioinformatics, Institute of Physiology, Charité Universitätsmedizin Berlin, Berlin, Germany., Willson TM; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jazyk: angličtina
Zdroj: Nature reviews. Chemistry [Nat Rev Chem] 2022 Apr; Vol. 6 (4), pp. 287-295. Date of Electronic Publication: 2022 Feb 15.
DOI: 10.1038/s41570-022-00363-z
Abstrakt: One aspirational goal of computational chemistry is to predict potent and drug-like binders for any protein, such that only those that bind are synthesized. In this Roadmap, we describe the launch of Critical Assessment of Computational Hit-finding Experiments (CACHE), a public benchmarking project to compare and improve small molecule hit-finding algorithms through cycles of prediction and experimental testing. Participants will predict small molecule binders for new and biologically relevant protein targets representing different prediction scenarios. Predicted compounds will be tested rigorously in an experimental hub, and all predicted binders as well as all experimental screening data, including the chemical structures of experimentally tested compounds, will be made publicly available, and not subject to any intellectual property restrictions. The ability of a range of computational approaches to find novel binders will be evaluated, compared, and openly published. CACHE will launch 3 new benchmarking exercises every year. The outcomes will be better prediction methods, new small molecule binders for target proteins of importance for fundamental biology or drug discovery, and a major technological step towards achieving the goal of Target 2035, a global initiative to identify pharmacological probes for all human proteins.
Databáze: MEDLINE
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