{"id":"W3110265926","doi":"10.1101/2020.11.24.393405","title":"Fragment Binding to the Nsp3 Macrodomain of SARS-CoV-2 Identified Through Crystallographic Screening and Computational Docking","year":2020,"lang":"en","type":"preprint","venue":"bioRxiv (Cold Spring Harbor Laboratory)","topic":"RNA and protein synthesis mechanisms","field":"Biochemistry, Genetics and Molecular Biology","cited_by":41,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"SLAC National Accelerator Laboratory; Lawrence Berkeley National Laboratory; Basic Energy Sciences; National Institute of General Medical Sciences; Office of the President, University of California; Biological and Environmental Research; Advanced Research Projects Agency; University of California, San Francisco; Plexxikon; Office of Science; National Institutes of Health; Newcastle University; Ministero dello Sviluppo Economico; Brookhaven National Laboratory; Fundação de Amparo à Pesquisa do Estado de São Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Biotechnology and Biological Sciences Research Council; Wellcome Trust; Cancer Research UK; Defense Advanced Research Projects Agency; Ontario Ministry of Economic Development and Innovation; Pfizer; York University; European Federation of Pharmaceutical Industries and Associations; Merck KGaA; National Institute for Health and Care Research; Sandler Foundation; Magyar Tudományos Akadémia; Genome Canada; Diamond Light Source; Novartis Pharma; European Commission; U.S. Department of Energy; National Science Foundation","keywords":"Docking (animal); Binding site; Active site; Computational biology; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Chemotype; Coronavirus disease 2019 (COVID-19); Crystallography; Enzyme; Small molecule; Plasma protein binding; Chemistry; Stereochemistry; Biophysics; Biology; Biochemistry; Medicine; Infectious disease (medical specialty)","routes":{"ca_aff":false,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":true},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0001973355,0.001062133,0.0008976805,0.0004136474,0.0003993212,0.0005464747,0.0005690121,0.0003733113,0.0023462],"category_scores_gemma":[0.0003550209,0.0001825916,0.0004512448,0.0005495321,0.000225762,0.0001978806,0.0003621006,0.0003950107,0.0003802684],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0006248489,"about_ca_system_score_gemma":0.0006997302,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.004457524,"about_ca_topic_score_gemma":0.00575306,"domain_scores_codex":[0.9998816,0.00002519083,0.000006166424,0.00001998424,0.00004127112,0.00002576022],"domain_scores_gemma":[0.9999311,0.0000294872,0.00001047876,0.000006701036,0.00001098709,0.00001126624],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"simulation_or_modeling","study_design_gemma":"bench_or_experimental","study_design_scores_codex":[0.003116175,0.0008448231,0.01777254,0.0009594341,0.0003430643,0.002089367,0.0002035328,0.5290105,0.3953443,0.004497482,0.004231579,0.04158722],"study_design_scores_gemma":[0.0004603139,0.000897568,0.009085438,0.00004214404,0.0001637031,0.000444626,0.0002249465,0.8357329,0.1489,0.001139743,0.00285913,0.00004950278],"study_design_candidate":"bench_or_experimental","study_design_consensus":null,"genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9854264,0.0006509851,0.007300999,0.00009449578,0.000009733453,0.00008389541,0.002119106,0.0005229276,0.00379141],"genre_scores_gemma":[0.97571,0.0006323314,0.01737501,0.00005327235,0.000004151881,0.0001036995,0.005176056,0.00005389594,0.0008916507],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.004457524,"threshold_uncertainty_score":0.008863151,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.02836841892363681,"score_gpt":0.2552413909227888,"score_spread":0.226872971999152,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}