{"doi":"10.1021/acs.jmedchem.5b02041","title":"Delineation of Polypharmacology across the Human Structural Kinome Using a Functional Site Interaction Fingerprint Approach","abstract":"Targeted polypharmacology of kinases has emerged as a promising strategy to design efficient and safe therapeutics. Here, we perform a systematic study of kinase-ligand binding modes for the human structural kinome at scale (208 kinases, 1777 unique ligands, and their complexes) by integrating chemical genomics and structural genomics data and by introducing a functional site interaction fingerprint (Fs-IFP) method. New insights into kinase-ligand binding modes were obtained. We establish relationships between the features of binding modes, the ligands, and the binding pockets, respectively. We also drive the intrinsic binding specificity and which correlation with amino acid conservation. Third, we explore the landscape of the binding modes and highlight the regions of \"selectivity pocket\" and \"selectivity entrance\". Finally, we demonstrate that Fs-IFP similarity is directly correlated to the experimentally determined profile. These improve our understanding of kinase-ligand interactions and contribute to the design of novel polypharmacological therapies targeting kinases.","journal":"Journal of Medicinal Chemistry","year":2016,"id":7179,"datarank":1.8549164826293465,"base_score":4.007333185232471,"endowment":4.007333185232471,"self_citation_contribution":0.6010999777848708,"citation_network_contribution":1.2538165048444756,"self_endowment_contribution":0.6010999777848708,"citer_contribution":1.2538165048444756,"corpus_percentile":null,"corpus_rank":null,"citation_count":54,"citer_count":32,"citers_with_citation_signal":30,"citers_with_endowment":30,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0494,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2016-03-17","fair_score":55.0,"fair_percentile":77.6,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":153,"name":"Li Xie","orcid":"0000-0003-3658-2535","position":1,"is_corresponding":false},{"id":150,"name":"Lei Xie","orcid":"0000-0001-9051-2111","position":2,"is_corresponding":false},{"id":125,"name":"Philip  E. Bourne","orcid":"0000-0002-7618-7292","position":3,"is_corresponding":false},{"id":293,"name":"Zheng Zhao","orcid":"0000-0003-1453-3230","position":0,"is_corresponding":true}],"reference_count":103,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":100.0,"fair_a":70.0,"fair_i":50.0,"fair_r":0.0,"fair_zscore":null,"fair_rationale":{"fair_score":55.0,"has_llm":false,"dimensions":{"F":{"name":"Findable","score":100.0,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"datacite=0, pmcid=True, pmid=True","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"OpenAlex id present","rationale":null}]},"A":{"name":"Accessible","score":70.0,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":0.5,"signal":"files/OA location present but not flagged OA","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"6 OA location(s)","rationale":null}]},"I":{"name":"Interoperable","score":50.0,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"accessions=1, trials=0","rationale":null}]},"R":{"name":"Reusable","score":0.0,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"not a dataset","rationale":null}]}},"suggestions":["Attach a clear, open reuse license (e.g. CC-BY or CC0).","Link the underlying datasets via DOIs / DataCite relations.","Maintain explicit versioning for the dataset.","Make the paper/data Open Access or deposit the files in an open repository."],"model":null,"agent_version":"fair_agent_v3","fulltext_source":"abstract_only"},"fair_model":null,"fair_agent_version":"fair_agent_v3","fair_fulltext_source":"abstract_only","fair_has_llm":false,"fair_computed_at":"2026-06-28T13:55:52.762182Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}