{"doi":"10.1371/journal.pone.0179936","title":"Insights into the binding mode of MEK type-III inhibitors. A step towards discovering and designing allosteric kinase inhibitors across the human kinome","abstract":"Protein kinases are critical drug targets for treating a large variety of human diseases. Type-III kinase inhibitors have attracted increasing attention as highly selective therapeutics. Thus, understanding the binding mechanism of existing type-III kinase inhibitors provides useful insights into designing new type-III kinase inhibitors. In this work, we have systematically studied the binding mode of MEK-targeted type-III inhibitors using structural systems pharmacology and molecular dynamics simulation. Our studies provide detailed sequence, structure, interaction-fingerprint, pharmacophore and binding-site information on the binding characteristics of MEK type-III kinase inhibitors. We hypothesize that the helix-folding activation loop is a hallmark allosteric binding site for type-III inhibitors. Subsequently, we screened and predicted allosteric binding sites across the human kinome, suggesting other kinases as potential targets suitable for type-III inhibitors.","journal":"PLOS ONE","year":2017,"id":340,"datarank":2.1880186369369765,"base_score":3.8712010109078907,"endowment":3.8712010109078907,"self_citation_contribution":0.5806801516361837,"citation_network_contribution":1.6073384853007928,"self_endowment_contribution":0.5806801516361837,"citer_contribution":1.6073384853007928,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":35,"citers_with_citation_signal":31,"citers_with_endowment":31,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2017-06-19","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":150,"name":"Lei Xie","orcid":"0000-0001-9051-2111","position":1,"is_corresponding":false},{"id":125,"name":"Philip  E. Bourne","orcid":"0000-0002-7618-7292","position":2,"is_corresponding":false},{"id":293,"name":"Zheng Zhao","orcid":"0000-0003-1453-3230","position":0,"is_corresponding":true}],"reference_count":49,"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":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":[]}