{"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":"codex-gemma-dda1882f352a","candidate_categories":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.0005995205,0.0004006559,0.0003993946,0.0001109756,0.0002166858,0.0001597814,0.0005393821,0.0003400862,0.000007006769],"category_scores_gemma":[0.000144175,0.0003745656,0.0001767565,0.0002850604,0.0001168245,0.000009863938,0.0009167673,0.000282584,0.000005410154],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0000222341,"about_ca_system_score_gemma":0.0001269839,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00004661071,"about_ca_topic_score_gemma":0.000003531718,"domain_scores_codex":[0.9977027,0.0001961876,0.0004867024,0.0008964114,0.0003607102,0.0003573079],"domain_scores_gemma":[0.9985757,0.00004475763,0.0003847149,0.0006894086,0.0002028208,0.0001025949],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"bench_or_experimental","study_design_scores_codex":[0.00005916301,0.00002729378,0.0004950148,0.0001502737,0.0002717077,0.00001119362,0.00004012049,0.0004106612,0.9976819,0.0006256796,0.0002184828,0.000008556905],"study_design_scores_gemma":[0.0002961982,0.00009153048,0.004053221,0.0002992158,0.00008590527,6.436419e-8,0.00002053273,0.000143022,0.9912943,0.00003263577,0.003230981,0.000452432],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.8718863,0.001201597,0.1250444,0.0005460315,0.0003659199,0.0007338204,0.0001734136,0.00004224418,0.000006227517],"genre_scores_gemma":[0.969868,0.0001009994,0.02899692,0.0005298409,0.000280153,0.0001424318,0.000002235229,0.00007787166,0.000001552367],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.09798166,"threshold_uncertainty_score":0.9998706,"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."}}