{"id":"W2975107521","doi":"10.1101/442806","title":"Rapid covalent-probe discovery by electrophile fragment screening","year":2018,"lang":"en","type":"preprint","venue":"bioRxiv (Cold Spring Harbor Laboratory)","topic":"Click Chemistry and Applications","field":"Chemistry","cited_by":17,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Israel Science Foundation; Pfizer; Rising Tide Foundation; Ontario Genomics; Ontario Ministry of Research, Innovation and Science; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; Genome Canada; Fundação de Amparo à Pesquisa do Estado de São Paulo; Novartis Pharma; Ontario Genomics Institute; European Federation of Pharmaceutical Industries and Associations; Merck KGaA","keywords":"Electrophile; Chemistry; Covalent bond; Combinatorial chemistry; Ligand efficiency; Fragment (logic); Ligand (biochemistry); Drug discovery; Cysteine; Selectivity; Deubiquitinating enzyme; Stereochemistry; High-throughput screening; Enzyme; Biochemistry; Organic chemistry; Gene; Receptor; Computer science; Ubiquitin","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":[0.001415135,0.0009581576,0.0006206255,0.0006596628,0.000302541,0.0006669359,0.0006210136,0.0005097506,0.003738821],"category_scores_gemma":[0.0009070426,0.0003267531,0.0004733177,0.0006340871,0.0004199306,0.0006264063,0.0007620277,0.0008826299,0.001184718],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0004594252,"about_ca_system_score_gemma":0.0002606726,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0002700125,"about_ca_topic_score_gemma":0.0006244646,"domain_scores_codex":[0.9992797,0.000163342,0.00004891259,0.0001579989,0.0002269248,0.0001231383],"domain_scores_gemma":[0.999516,0.0001733819,0.00008744736,0.0001053583,0.00006892947,0.00004882348],"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":[0.0001859576,0.00009223699,0.0003618511,0.0001458409,0.0000386512,0.0001944993,0.00005394316,0.0008607816,0.9788325,0.0009498281,0.0005010907,0.01778284],"study_design_scores_gemma":[0.0000173399,0.0004055764,0.0003529602,0.000004368903,0.00001751116,0.0001852014,0.00000915594,0.0009640527,0.9937417,0.0001550848,0.004135507,0.0000116145],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.7253701,0.005099047,0.2491364,0.0004347085,0.0001086445,0.0011859,0.002129744,0.002532455,0.01400303],"genre_scores_gemma":[0.9282659,0.002561236,0.05682903,0.0002181378,0.00003645722,0.0005197122,0.001688162,0.0002113848,0.009669952],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.003738821,"threshold_uncertainty_score":0.01250762,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01440558281832885,"score_gpt":0.2214086189432059,"score_spread":0.207003036124877,"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."}}