{"doi":"10.1021/acs.jcim.3c00347","title":"A Hybrid Structure-Based Machine Learning Approach for Predicting Kinase Inhibition by Small Molecules","abstract":"Kinases have been the focus of drug discovery programs for three decades leading to over 70 therapeutic kinase inhibitors and biophysical affinity measurements for over 130,000 kinase-compound pairs. Nonetheless, the precise target spectrum for many kinases remains only partly understood. In this study, we describe a computational approach to unlocking qualitative and quantitative kinome-wide binding measurements for structure-based machine learning. Our study has three components: (i) a Kinase Inhibitor Complex (KinCo) data set comprising in silico predicted kinase structures paired with experimental binding constants, (ii) a machine learning loss function that integrates qualitative and quantitative data for model training, and (iii) a structure-based machine learning model trained on KinCo. We show that our approach outperforms methods trained on crystal structures alone in predicting binary and quantitative kinase-compound interaction affinities; relative to structure-free methods, our approach also captures known kinase biochemistry and more successfully generalizes to distant kinase sequences and compound scaffolds.","journal":"Journal of Chemical Information and Modeling","year":2023,"id":336499,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.94,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":493478,"name":"Peter S. Kutchukian","orcid":"0000-0002-5684-1971","position":1,"is_corresponding":false},{"id":1066942,"name":"Nhan Duc Nguyen","orcid":"0000-0002-5976-0819","position":2,"is_corresponding":false},{"id":552754,"name":"Mohammed AlQuraishi","orcid":"0000-0001-6817-1322","position":3,"is_corresponding":false},{"id":24147,"name":"Peter K. Sorger","orcid":"0000-0002-3364-1838","position":4,"is_corresponding":false},{"id":256022,"name":"Changchang Liu","orcid":"0000-0003-4594-4577","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T01:10:17.243221Z","pmid":"37595065","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}