{"id":"https://openalex.org/W7213288244","doi":"https://doi.org/10.1021/acs.jpclett.6c02620","title":"Impact of Inhibitor Size and Flexibility on the Binding Pathways to c-Src Kinase","display_name":"Impact of Inhibitor Size and Flexibility on the Binding Pathways to c-Src Kinase","publication_year":2026,"publication_date":"2026-09-15","ids":{"openalex":"https://openalex.org/W7213288244","doi":"https://doi.org/10.1021/acs.jpclett.6c02620","pmid":"https://pubmed.ncbi.nlm.nih.gov/42917142","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13637072"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jpclett.6c02620","doi":"https://doi.org/10.1021/acs.jpclett.6c02620","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jpclett.6c02620","pdf_url":"https://pubs.acs.org/jpclcd/article-pdf/17/39/11119/68525257/acs.jpclett.6c02620.pdf","source":{"id":"https://openalex.org/S123480357","display_name":"The Journal of Physical Chemistry Letters","issn_l":"1948-7185","issn":["1948-7185"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-1","medline","norway-1","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Physical Chemistry Letters","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://pubs.acs.org/jpclcd/article-pdf/17/39/11119/68525257/acs.jpclett.6c02620.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5090328150","display_name":"Ai Shinobu","orcid":"https://orcid.org/0000-0002-2865-6461","observed_orcids":["https://orcid.org/0000-0002-2865-6461"]},"institutions":[{"id":"https://openalex.org/I4210116810","display_name":"RIKEN Center for Biosystems Dynamics Research","ror":"https://ror.org/023rffy11","country_code":"JP","type":"facility","lineage":["https://openalex.org/I4210110652","https://openalex.org/I4210116810"]},{"id":"https://openalex.org/I98285908","display_name":"The University of Osaka","ror":"https://ror.org/035t8zc32","country_code":"JP","type":"education","lineage":["https://openalex.org/I98285908"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Ai Shinobu","raw_affiliation_strings":["RIKEN Center for Biosystems Dynamics Research , 7-1-26 minatojima-minamimachi, Chuo-ku , , ,","The University of Osaka , , 2-8 Yamadaoka, Suita , , ,"],"raw_orcid":"https://orcid.org/0000-0002-2865-6461","affiliations":[{"raw_affiliation_string":"RIKEN Center for Biosystems Dynamics Research , 7-1-26 minatojima-minamimachi, Chuo-ku , , ,","institution_ids":["https://openalex.org/I4210116810"]},{"raw_affiliation_string":"The University of Osaka , , 2-8 Yamadaoka, Suita , , ,","institution_ids":["https://openalex.org/I98285908"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014335328","display_name":"Suyong Re","orcid":"https://orcid.org/0000-0002-3752-6554","observed_orcids":["https://orcid.org/0000-0002-3752-6554"]},"institutions":[{"id":"https://openalex.org/I4210086383","display_name":"National Institute of Biomedical Innovation, Health and Nutrition","ror":"https://ror.org/001rkbe13","country_code":"JP","type":"facility","lineage":["https://openalex.org/I4210086383"]},{"id":"https://openalex.org/I4210116810","display_name":"RIKEN Center for Biosystems Dynamics Research","ror":"https://ror.org/023rffy11","country_code":"JP","type":"facility","lineage":["https://openalex.org/I4210110652","https://openalex.org/I4210116810"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Suyong Re","raw_affiliation_strings":["National Institutes of Biomedical Innovation, Health, and Nutrition , , 3-17 Senrioka Shinmachi, Settu-shi , ,","RIKEN Center for Biosystems Dynamics Research , 7-1-26 minatojima-minamimachi, Chuo-ku , , ,"],"raw_orcid":"https://orcid.org/0000-0002-3752-6554","affiliations":[{"raw_affiliation_string":"National Institutes of Biomedical Innovation, Health, and Nutrition , , 3-17 Senrioka Shinmachi, Settu-shi , ,","institution_ids":["https://openalex.org/I4210086383"]},{"raw_affiliation_string":"RIKEN Center for Biosystems Dynamics Research , 7-1-26 minatojima-minamimachi, Chuo-ku , , ,","institution_ids":["https://openalex.org/I4210116810"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022935528","display_name":"Hiraku Oshima","orcid":"https://orcid.org/0000-0001-5626-1291","observed_orcids":["https://orcid.org/0000-0001-5626-1291"]},"institutions":[{"id":"https://openalex.org/I180941496","display_name":"University of Hyogo","ror":"https://ror.org/0151bmh98","country_code":"JP","type":"education","lineage":["https://openalex.org/I180941496"]},{"id":"https://openalex.org/I4210116810","display_name":"RIKEN Center for Biosystems Dynamics Research","ror":"https://ror.org/023rffy11","country_code":"JP","type":"facility","lineage":["https://openalex.org/I4210110652","https://openalex.org/I4210116810"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Hiraku Oshima","raw_affiliation_strings":["RIKEN Center for Biosystems Dynamics Research , 7-1-26 minatojima-minamimachi, Chuo-ku , , ,","University of Hyogo , , 3-2-1 Kouto, Kamigori-cho , , ,"],"raw_orcid":"https://orcid.org/0000-0001-5626-1291","affiliations":[{"raw_affiliation_string":"RIKEN Center for Biosystems Dynamics Research , 7-1-26 minatojima-minamimachi, Chuo-ku , , ,","institution_ids":["https://openalex.org/I4210116810"]},{"raw_affiliation_string":"University of Hyogo , , 3-2-1 Kouto, Kamigori-cho , , ,","institution_ids":["https://openalex.org/I180941496"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5074728289","display_name":"Yuji Sugita","orcid":"https://orcid.org/0000-0001-9738-9216","observed_orcids":["https://orcid.org/0000-0001-9738-9216"]},"institutions":[{"id":"https://openalex.org/I4210116810","display_name":"RIKEN Center for Biosystems Dynamics Research","ror":"https://ror.org/023rffy11","country_code":"JP","type":"facility","lineage":["https://openalex.org/I4210110652","https://openalex.org/I4210116810"]},{"id":"https://openalex.org/I4210129730","display_name":"RIKEN Center for Computational Science","ror":"https://ror.org/03r519674","country_code":"JP","type":"facility","lineage":["https://openalex.org/I4210110652","https://openalex.org/I4210129730"]},{"id":"https://openalex.org/I4405286309","display_name":"RIKEN Pioneering Research Institute","ror":"https://ror.org/01s6zhz21","country_code":"JP","type":"facility","lineage":["https://openalex.org/I4210110652","https://openalex.org/I4405286309"]},{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Yuji Sugita","raw_affiliation_strings":["RIKEN Center for Biosystems Dynamics Research , 7-1-26 minatojima-minamimachi, Chuo-ku , , ,","RIKEN Center for Computational Science , 7-1-26 minatojima-minamimachi, Chuo-ku , , ,","RIKEN Pioneering Research Institute , , 2-1 Hirosawa, Wako , ,","University of Tokyo , , 7-3-1 Hongo, Bunkyo-ku , ,"],"raw_orcid":"https://orcid.org/0000-0001-9738-9216","affiliations":[{"raw_affiliation_string":"RIKEN Center for Biosystems Dynamics Research , 7-1-26 minatojima-minamimachi, Chuo-ku , , ,","institution_ids":["https://openalex.org/I4210116810"]},{"raw_affiliation_string":"RIKEN Center for Computational Science , 7-1-26 minatojima-minamimachi, Chuo-ku , , ,","institution_ids":["https://openalex.org/I4210129730"]},{"raw_affiliation_string":"RIKEN Pioneering Research Institute , , 2-1 Hirosawa, Wako , ,","institution_ids":["https://openalex.org/I4405286309"]},{"raw_affiliation_string":"University of Tokyo , , 7-3-1 Hongo, Bunkyo-ku , ,","institution_ids":["https://openalex.org/I74801974"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":7,"corresponding_author_ids":["https://openalex.org/A5074728289"],"corresponding_institution_ids":["https://openalex.org/I4210116810","https://openalex.org/I4210129730","https://openalex.org/I4405286309","https://openalex.org/I74801974"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":{"value":4500,"currency":"USD","value_usd":4500},"fwci":1.5377,"has_fulltext":true,"cited_by_count":1,"citation_normalized_percentile":{"value":0.87132963,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":92,"max":95},"biblio":{"volume":"17","issue":"39","first_page":"11119","last_page":"11128"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.5985999703407288,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.5985999703407288,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.3792000114917755,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.010499999858438969,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/c-src-kinase","display_name":"c-Src kinase","score":1.0},{"id":"https://openalex.org/keywords/dasatinib","display_name":"dasatinib","score":0.7519999742507935},{"id":"https://openalex.org/keywords/protein-phosphatase-1","display_name":"protein phosphatase 1","score":0.8230000138282776},{"id":"https://openalex.org/keywords/kinase-inhibitor-binding","display_name":"kinase inhibitor binding","score":0.7160000205039978},{"id":"https://openalex.org/keywords/binding-pathway","display_name":"binding pathway","score":0.7889999747276306},{"id":"https://openalex.org/keywords/conformational-plasticity","display_name":"conformational plasticity","score":0.8489999771118164},{"id":"https://openalex.org/keywords/free-energy-profiles","display_name":"free energy profiles","score":0.6489999890327454},{"id":"https://openalex.org/keywords/salt-bridges","display_name":"salt bridges","score":0.6759999990463257},{"id":"https://openalex.org/keywords/binding-kinetics","display_name":"binding kinetics","score":0.5479999780654907}],"concepts":[{"id":"https://openalex.org/C2780598303","wikidata":"https://www.wikidata.org/wiki/Q65921492","display_name":"Flexibility (engineering)","level":2,"score":0.7366999983787537},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.582099974155426},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.5715000033378601},{"id":"https://openalex.org/C18705241","wikidata":"https://www.wikidata.org/wiki/Q1128023","display_name":"Conformational isomerism","level":3,"score":0.5669000148773193},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.5486000180244446},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.524399995803833},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.5091999769210815},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.5008000135421753},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.3693999946117401},{"id":"https://openalex.org/C2779536868","wikidata":"https://www.wikidata.org/wiki/Q419940","display_name":"Dasatinib","level":4,"score":0.3693999946117401},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.35499998927116394},{"id":"https://openalex.org/C2777936996","wikidata":"https://www.wikidata.org/wiki/Q17148461","display_name":"Conformational ensembles","level":3,"score":0.3456999957561493},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.33160001039505005},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.325300008058548},{"id":"https://openalex.org/C145912823","wikidata":"https://www.wikidata.org/wiki/Q113558","display_name":"Dynamics (music)","level":2,"score":0.3165000081062317},{"id":"https://openalex.org/C2777339483","wikidata":"https://www.wikidata.org/wiki/Q647203","display_name":"Conformational change","level":2,"score":0.31040000915527344},{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.30720001459121704},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2906000018119812},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.2883000075817108},{"id":"https://openalex.org/C553089730","wikidata":"https://www.wikidata.org/wiki/Q4914021","display_name":"Binding protein","level":3,"score":0.28029999136924744},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.2797999978065491},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.2718999981880188},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.2696000039577484},{"id":"https://openalex.org/C2775981520","wikidata":"https://www.wikidata.org/wiki/Q17156992","display_name":"Protein dynamics","level":3,"score":0.2671999931335449},{"id":"https://openalex.org/C3020299119","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Binding pocket","level":3,"score":0.25760000944137573},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2547999918460846},{"id":"https://openalex.org/C196347352","wikidata":"https://www.wikidata.org/wiki/Q24771787","display_name":"SH3 domain","level":4,"score":0.25200000405311584}],"mesh":[{"descriptor_ui":"D000069439","descriptor_name":"Dasatinib","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D000081247","descriptor_name":"CSK Tyrosine-Protein Kinase","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011720","descriptor_name":"Pyrazoles","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019061","descriptor_name":"src-Family Kinases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D019061","descriptor_name":"src-Family Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019061","descriptor_name":"src-Family Kinases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1021/acs.jpclett.6c02620","doi":"https://doi.org/10.1021/acs.jpclett.6c02620","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jpclett.6c02620","pdf_url":"https://pubs.acs.org/jpclcd/article-pdf/17/39/11119/68525257/acs.jpclett.6c02620.pdf","source":{"id":"https://openalex.org/S123480357","display_name":"The Journal of Physical Chemistry Letters","issn_l":"1948-7185","issn":["1948-7185"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-1","medline","norway-1","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Physical Chemistry Letters","raw_type":"journal-article"},{"id":"doi:10.1101/2022.10.25.513784","doi":"https://doi.org/10.1101/2022.10.25.513784","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2022.10.25.513784","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2022/10/26/2022.10.25.513784.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},{"id":"pmid:42917142","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42917142","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The journal of physical chemistry letters","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13637072","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13637072/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"J Phys Chem Lett","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1021/acs.jpclett.6c02620","doi":"https://doi.org/10.1021/acs.jpclett.6c02620","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jpclett.6c02620","pdf_url":"https://pubs.acs.org/jpclcd/article-pdf/17/39/11119/68525257/acs.jpclett.6c02620.pdf","source":{"id":"https://openalex.org/S123480357","display_name":"The Journal of Physical Chemistry Letters","issn_l":"1948-7185","issn":["1948-7185"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-1","medline","norway-1","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Physical Chemistry Letters","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G1153619429","display_name":null,"funder_award_id":"hp200129","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G1527142388","display_name":null,"funder_award_id":"JPMXP1020200101","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G1709759425","display_name":null,"funder_award_id":"JPMXP1020230120","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G2047533555","display_name":"Prediction of long-time biomolecular dynamics using data assimilation and enhanced sampling methods","funder_award_id":"20K06582","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G2073131814","display_name":"\u7d30\u80de\u8868\u9762\u7cd6\u9396\u30af\u30e9\u30b9\u30bf\u30fc\u306e\u69cb\u9020\u2015\u6a5f\u80fd\u76f8\u95a2\u3068\u4e88\u6e2c\u57fa\u76e4\u306e\u958b\u767a","funder_award_id":"24K03041","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G2719384493","display_name":null,"funder_award_id":"19H05645","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G2991958618","display_name":null,"funder_award_id":"21H05249","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G304576431","display_name":null,"funder_award_id":"JPMXP1020200101","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G3796416943","display_name":"3D Structure prediction of glycan clusters and its application for vaccine design","funder_award_id":"19K12229","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G4150949267","display_name":null,"funder_award_id":"hp210172","funder_id":"https://openalex.org/F4320335125","funder_display_name":"RIKEN"},{"id":"https://openalex.org/G4332620356","display_name":null,"funder_award_id":"hp210177","funder_id":"https://openalex.org/F4320335125","funder_display_name":"RIKEN"},{"id":"https://openalex.org/G4910619891","display_name":null,"funder_award_id":"hp200129","funder_id":"https://openalex.org/F4320335125","funder_display_name":"RIKEN"},{"id":"https://openalex.org/G5046756818","display_name":null,"funder_award_id":"hp210177","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G5176219108","display_name":null,"funder_award_id":"19H05645","funder_id":"https://openalex.org/F4320335125","funder_display_name":"RIKEN"},{"id":"https://openalex.org/G532248676","display_name":null,"funder_award_id":"JPMXP1020200101","funder_id":"https://openalex.org/F4320335125","funder_display_name":"RIKEN"},{"id":"https://openalex.org/G5345629513","display_name":null,"funder_award_id":"hp220164","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G6270203833","display_name":null,"funder_award_id":"hp230216","funder_id":"https://openalex.org/F4320335125","funder_display_name":"RIKEN"},{"id":"https://openalex.org/G6733093587","display_name":null,"funder_award_id":"HP220170","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G7122904584","display_name":null,"funder_award_id":"21H05249","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G7177253478","display_name":null,"funder_award_id":"JPMXP1020200201","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G7493608361","display_name":null,"funder_award_id":"hp210172","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G7574485952","display_name":null,"funder_award_id":"hp200135","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G760910490","display_name":"Multi-scale molecular dynamics simulation on biomolecular dynamics in crowded cellular environments","funder_award_id":"19H05645","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G8389989449","display_name":null,"funder_award_id":"hp200135","funder_id":"https://openalex.org/F4320335125","funder_display_name":"RIKEN"},{"id":"https://openalex.org/G8485512905","display_name":null,"funder_award_id":"19K12229","funder_id":"https://openalex.org/F4320335125","funder_display_name":"RIKEN"},{"id":"https://openalex.org/G8949051751","display_name":null,"funder_award_id":"JPMXP1020200201","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"},{"id":"https://openalex.org/G8962970800","display_name":null,"funder_award_id":"19K12229","funder_id":"https://openalex.org/F4320320912","funder_display_name":"Ministry of Education, Culture, Sports, Science and Technology"}],"funders":[{"id":"https://openalex.org/F4320320912","display_name":"Ministry of Education, Culture, Sports, Science and Technology","ror":"https://ror.org/048rj2z13"},{"id":"https://openalex.org/F4320334764","display_name":"Japan Society for the Promotion of Science","ror":"https://ror.org/00hhkn466"},{"id":"https://openalex.org/F4320335125","display_name":"RIKEN","ror":"https://ror.org/01sjwvz98"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7213288244.pdf","grobid_xml":"https://content.openalex.org/works/W7213288244.grobid-xml"},"referenced_works_count":63,"referenced_works":["https://openalex.org/W1508256447","https://openalex.org/W1976499671","https://openalex.org/W1978607920","https://openalex.org/W1989814214","https://openalex.org/W1990524359","https://openalex.org/W2017835622","https://openalex.org/W2021019774","https://openalex.org/W2035687084","https://openalex.org/W2040809566","https://openalex.org/W2043789128","https://openalex.org/W2048633418","https://openalex.org/W2055648985","https://openalex.org/W2057477511","https://openalex.org/W2067174909","https://openalex.org/W2067191435","https://openalex.org/W2072456220","https://openalex.org/W2074140794","https://openalex.org/W2082170965","https://openalex.org/W2088806906","https://openalex.org/W2090895449","https://openalex.org/W2103945336","https://openalex.org/W2105649494","https://openalex.org/W2106140689","https://openalex.org/W2128824543","https://openalex.org/W2131174104","https://openalex.org/W2144288821","https://openalex.org/W2147993766","https://openalex.org/W2161605421","https://openalex.org/W2271736303","https://openalex.org/W2342304607","https://openalex.org/W2598374175","https://openalex.org/W2606956542","https://openalex.org/W2609417898","https://openalex.org/W2620254666","https://openalex.org/W2737764894","https://openalex.org/W2767492466","https://openalex.org/W2800801983","https://openalex.org/W2892745578","https://openalex.org/W2950292741","https://openalex.org/W2970445901","https://openalex.org/W2998628971","https://openalex.org/W3033827960","https://openalex.org/W3065109437","https://openalex.org/W3080322320","https://openalex.org/W3089408272","https://openalex.org/W3096716632","https://openalex.org/W3159652793","https://openalex.org/W3161074857","https://openalex.org/W3176856228","https://openalex.org/W3186131367","https://openalex.org/W3189949217","https://openalex.org/W3195811056","https://openalex.org/W3203420675","https://openalex.org/W3207731997","https://openalex.org/W3214278476","https://openalex.org/W4205133697","https://openalex.org/W4225122578","https://openalex.org/W4226055301","https://openalex.org/W4255486780","https://openalex.org/W4382501570","https://openalex.org/W4386526027","https://openalex.org/W4387440676","https://openalex.org/W4412723379"],"related_works":["https://openalex.org/W4307446582","https://openalex.org/W4319936766","https://openalex.org/W3195811056","https://openalex.org/W1980715840","https://openalex.org/W2321173906","https://openalex.org/W3168074431","https://openalex.org/W2560807575","https://openalex.org/W2970445901","https://openalex.org/W2153342471","https://openalex.org/W145927069"],"abstract_inverted_index":{"ABSTRACT":[0],"Considering":[1],"dynamical":[2],"aspects":[3],"of":[4,17,26,57,108,132,193,201],"protein-drug":[5],"binding":[6,104,122,134,138,220],"processes":[7],"is":[8,62,148],"inevitable":[9],"in":[10,101,119,150],"current":[11],"drug":[12,58],"compound":[13,59],"design.":[14],"Conformational":[15,170],"plasticity":[16],"protein":[18,41],"kinases":[19],"poses":[20,139],"a":[21,48,87,92,129],"challenge":[22],"for":[23,54,143,180],"the":[24,55,125,136,164,167,206,219],"design":[25],"their":[27,151],"inhibitors,":[28],"and":[29,90,105,177,198,216],"therefore,":[30],"atomistic":[31],"molecular":[32],"dynamics":[33],"(MD)":[34],"simulations":[35,75,100],"have":[36,44],"often":[37],"been":[38,45],"utilized.":[39],"While":[40,124],"conformational":[42],"changes":[43],"increasingly":[46],"discussed,":[47],"fundamental":[49],"yet":[50],"non-trivial":[51],"question":[52],"remains":[53],"effect":[56],"flexibility,":[60],"which":[61,181,222],"hardly":[63],"detectable":[64],"from":[65],"experiments.":[66],"In":[67],"this":[68],"study,":[69],"we":[70],"apply":[71],"two-dimensional":[72],"replica-exchange":[73],"MD":[74,116],"as":[76],"enhanced":[77],"sampling":[78],"to":[79,162],"investigate":[80],"how":[81],"c-Src":[82],"kinase":[83],"can":[84],"bind":[85],"PP1,":[86],"small":[88],"inhibitor,":[89],"dasatinib,":[91],"larger":[93],"inhibitor":[94,214,226],"with":[95],"greater":[96],"flexibility.":[97],"600":[98],"microseconds":[99],"total":[102],"sample":[103],"unbinding":[106],"events":[107],"these":[109],"inhibitors":[110,127],"much":[111],"more":[112,159],"frequently":[113],"than":[114,160],"conventional":[115],"simulation,":[117],"resulting":[118],"statistically":[120],"converged":[121],"pathways.":[123],"two":[126],"adopt":[128],"similar":[130],"mechanism":[131],"multiple":[133],"pathways,":[135],"non-canonical":[137],"become":[140],"less":[141],"feasible":[142],"dasatinib.":[144],"A":[145],"notable":[146],"difference":[147],"apparent":[149],"energetics":[152],"where":[153],"dasatinib":[154,174,194],"stabilizes":[155],"at":[156,195],"intermediate":[157,196],"states":[158],"PP1":[161],"raise":[163],"barrier":[165],"toward":[166],"canonical":[168],"pose.":[169],"analysis":[171],"shows":[172],"that":[173,213],"adopts":[175],"linear":[176],"bent":[178],"forms":[179],"relative":[182],"populations":[183],"are":[184],"altered":[185],"upon":[186],"binding.":[187],"We":[188],"further":[189],"find":[190],"hidden":[191],"conformations":[192],"regions,":[197],"unexpectedly":[199],"one":[200],"them":[202],"could":[203,223],"efficiently":[204],"bypasses":[205],"intermediate-to-bound":[207],"state":[208],"transition.":[209],"The":[210],"results":[211],"demonstrate":[212],"size":[215],"flexibility":[217],"impact":[218],"mechanism,":[221],"potentially":[224],"modulate":[225],"residence":[227],"time.":[228]},"counts_by_year":[{"year":2026,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-09-16T00:00:00"}
