{"id":"https://openalex.org/W4389505974","doi":"https://doi.org/10.1021/acs.jcim.3c01352","title":"Conformational Selectivity of ITK Inhibitors: Insights from Molecular Dynamics Simulations","display_name":"Conformational Selectivity of ITK Inhibitors: Insights from Molecular Dynamics Simulations","publication_year":2023,"publication_date":"2023-12-09","ids":{"openalex":"https://openalex.org/W4389505974","doi":"https://doi.org/10.1021/acs.jcim.3c01352","pmid":"https://pubmed.ncbi.nlm.nih.gov/38069816"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.3c01352","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c01352","pdf_url":"https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.3c01352","source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"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":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.3c01352","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5102974481","display_name":"Naoki Ogawa","orcid":"https://orcid.org/0000-0002-0899-1721"},"institutions":[{"id":"https://openalex.org/I4210108598","display_name":"Japan Tobacco (Japan)","ror":"https://ror.org/01xdq1k91","country_code":"JP","type":"company","lineage":["https://openalex.org/I4210108598"]},{"id":"https://openalex.org/I89630735","display_name":"Yokohama City University","ror":"https://ror.org/0135d1r83","country_code":"JP","type":"education","lineage":["https://openalex.org/I89630735"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Naoki Ogawa","raw_affiliation_strings":["Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan","Graduate School of Medicinal Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan"],"raw_orcid":"https://orcid.org/0000-0002-0899-1721","affiliations":[{"raw_affiliation_string":"Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan","institution_ids":["https://openalex.org/I4210108598"]},{"raw_affiliation_string":"Graduate School of Medicinal Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan","institution_ids":["https://openalex.org/I89630735"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000011261","display_name":"Masateru Ohta","orcid":"https://orcid.org/0000-0002-6580-7185"},"institutions":[{"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"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Masateru Ohta","raw_affiliation_strings":["HPC- and AI-Driven Drug Development Platform Division, Center for Computational Science, RIKEN, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan"],"raw_orcid":"https://orcid.org/0000-0002-6580-7185","affiliations":[{"raw_affiliation_string":"HPC- and AI-Driven Drug Development Platform Division, Center for Computational Science, RIKEN, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan","institution_ids":["https://openalex.org/I4210129730"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5069786759","display_name":"Mitsunori Ikeguchi","orcid":"https://orcid.org/0000-0003-3199-6931"},"institutions":[{"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/I89630735","display_name":"Yokohama City University","ror":"https://ror.org/0135d1r83","country_code":"JP","type":"education","lineage":["https://openalex.org/I89630735"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Mitsunori Ikeguchi","raw_affiliation_strings":["Graduate School of Medicinal Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan","HPC- and AI-Driven Drug Development Platform Division, Center for Computational Science, RIKEN, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan"],"raw_orcid":"https://orcid.org/0000-0003-3199-6931","affiliations":[{"raw_affiliation_string":"Graduate School of Medicinal Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan","institution_ids":["https://openalex.org/I89630735"]},{"raw_affiliation_string":"HPC- and AI-Driven Drug Development Platform Division, Center for Computational Science, RIKEN, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan","institution_ids":["https://openalex.org/I4210129730"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5069786759"],"corresponding_institution_ids":["https://openalex.org/I4210129730","https://openalex.org/I89630735"],"apc_list":null,"apc_paid":null,"fwci":1.8711,"has_fulltext":true,"cited_by_count":9,"citation_normalized_percentile":{"value":0.86362755,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":95,"max":99},"biblio":{"volume":"63","issue":"24","first_page":"7860","last_page":"7872"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.9988999962806702,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.9988999962806702,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10031","display_name":"T-cell and B-cell Immunology","score":0.9973000288009644,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12477","display_name":"Toxin Mechanisms and Immunotoxins","score":0.9962999820709229,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.8031662702560425},{"id":"https://openalex.org/keywords/selectivity","display_name":"Selectivity","score":0.7169718146324158},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.6591271162033081},{"id":"https://openalex.org/keywords/free-energy-perturbation","display_name":"Free energy perturbation","score":0.5934560298919678},{"id":"https://openalex.org/keywords/binding-pocket","display_name":"Binding pocket","score":0.44605520367622375},{"id":"https://openalex.org/keywords/binding-site","display_name":"Binding site","score":0.4113297760486603},{"id":"https://openalex.org/keywords/biophysics","display_name":"Biophysics","score":0.3952064514160156},{"id":"https://openalex.org/keywords/stereochemistry","display_name":"Stereochemistry","score":0.37423086166381836},{"id":"https://openalex.org/keywords/combinatorial-chemistry","display_name":"Combinatorial chemistry","score":0.337127685546875},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.26807713508605957},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.2598104178905487},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.16807979345321655}],"concepts":[{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.8031662702560425},{"id":"https://openalex.org/C118792377","wikidata":"https://www.wikidata.org/wiki/Q108584245","display_name":"Selectivity","level":3,"score":0.7169718146324158},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6591271162033081},{"id":"https://openalex.org/C162641036","wikidata":"https://www.wikidata.org/wiki/Q5500215","display_name":"Free energy perturbation","level":3,"score":0.5934560298919678},{"id":"https://openalex.org/C3020299119","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Binding pocket","level":3,"score":0.44605520367622375},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.4113297760486603},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.3952064514160156},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.37423086166381836},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.337127685546875},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.26807713508605957},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.2598104178905487},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.16807979345321655},{"id":"https://openalex.org/C161790260","wikidata":"https://www.wikidata.org/wiki/Q82264","display_name":"Catalysis","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D008968","descriptor_name":"Molecular Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008968","descriptor_name":"Molecular Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008968","descriptor_name":"Molecular Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008968","descriptor_name":"Molecular Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008968","descriptor_name":"Molecular Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008968","descriptor_name":"Molecular Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"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":"Q000494","qualifier_name":"pharmacology","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":"Q000494","qualifier_name":"pharmacology","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":"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":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","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":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.3c01352","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c01352","pdf_url":"https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.3c01352","source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"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":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:38069816","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/38069816","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,"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":"Journal of chemical information and modeling","raw_type":null},{"id":"pmh:oai:pubmedcentral.nih.gov:10751800","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10751800","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10751800/pdf/ci3c01352.pdf","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,"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":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1021/acs.jcim.3c01352","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c01352","pdf_url":"https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.3c01352","source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"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":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/7","display_name":"Affordable and clean energy","score":0.5799999833106995}],"awards":[{"id":"https://openalex.org/G260256852","display_name":null,"funder_award_id":"JP22fk0310517","funder_id":"https://openalex.org/F4320311405","funder_display_name":"Japan Agency for Medical Research and Development"},{"id":"https://openalex.org/G2818062374","display_name":null,"funder_award_id":"SK202202","funder_id":"https://openalex.org/F4320317112","funder_display_name":"Yokohama City University"},{"id":"https://openalex.org/G3953835832","display_name":null,"funder_award_id":"SK202202","funder_id":"https://openalex.org/F4320311405","funder_display_name":"Japan Agency for Medical Research and Development"},{"id":"https://openalex.org/G7412970795","display_name":null,"funder_award_id":"JP23ama121023","funder_id":"https://openalex.org/F4320311405","funder_display_name":"Japan Agency for Medical Research and Development"}],"funders":[{"id":"https://openalex.org/F4320311405","display_name":"Japan Agency for Medical Research and Development","ror":"https://ror.org/004rtk039"},{"id":"https://openalex.org/F4320317112","display_name":"Yokohama City University","ror":"https://ror.org/0135d1r83"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4389505974.pdf","grobid_xml":"https://content.openalex.org/works/W4389505974.grobid-xml"},"referenced_works_count":47,"referenced_works":["https://openalex.org/W1491824558","https://openalex.org/W1952188797","https://openalex.org/W1967163463","https://openalex.org/W1969030265","https://openalex.org/W1969189143","https://openalex.org/W1972131667","https://openalex.org/W1976860932","https://openalex.org/W1984481443","https://openalex.org/W2003417987","https://openalex.org/W2012499988","https://openalex.org/W2019118611","https://openalex.org/W2021848632","https://openalex.org/W2026792857","https://openalex.org/W2029336928","https://openalex.org/W2030205108","https://openalex.org/W2040140683","https://openalex.org/W2045694062","https://openalex.org/W2052293344","https://openalex.org/W2052831496","https://openalex.org/W2072604508","https://openalex.org/W2082622773","https://openalex.org/W2086286404","https://openalex.org/W2086634221","https://openalex.org/W2092972397","https://openalex.org/W2094642095","https://openalex.org/W2097275791","https://openalex.org/W2106140689","https://openalex.org/W2135163046","https://openalex.org/W2138305674","https://openalex.org/W2154670681","https://openalex.org/W2154807028","https://openalex.org/W2167321693","https://openalex.org/W2299845867","https://openalex.org/W2480023505","https://openalex.org/W2802093589","https://openalex.org/W2802390800","https://openalex.org/W2866550058","https://openalex.org/W2912818999","https://openalex.org/W2954187991","https://openalex.org/W2989374524","https://openalex.org/W3098993911","https://openalex.org/W3167019654","https://openalex.org/W3179974334","https://openalex.org/W3216674381","https://openalex.org/W4211166631","https://openalex.org/W4317871134","https://openalex.org/W4376129086"],"related_works":["https://openalex.org/W2144327848","https://openalex.org/W3010939925","https://openalex.org/W2797856818","https://openalex.org/W4243768084","https://openalex.org/W2054248955","https://openalex.org/W4248966070","https://openalex.org/W2064287238","https://openalex.org/W4283765627","https://openalex.org/W1576999979","https://openalex.org/W4389505974"],"abstract_inverted_index":{"Interleukin-2-inducible":[0],"T-cell":[1,8],"kinase":[2],"(ITK)":[3],"regulates":[4],"the":[5,26,42,55,91,107,117,120,123,129,141,145,181,188],"response":[6],"to":[7,25,41,53,62,186],"receptor":[9],"signaling":[10],"and":[11,18,85,90,125,147,156,180],"is":[12,170],"a":[13],"drug":[14],"target":[15],"for":[16,48,79,166],"inflammatory":[17],"immunological":[19],"diseases.":[20],"Molecules":[21],"that":[22,38,140],"bind":[23,39],"preferentially":[24,40],"active":[27,84,124],"form":[28,44],"of":[29,58,88,104,106,122,144,149,190],"ITK":[30,66,193],"have":[31,45],"low":[32],"selectivity":[33,47,57,103],"between":[34],"kinases,":[35],"whereas":[36],"those":[37],"inactive":[43,86,126],"high":[46],"ITK.":[49],"Therefore,":[50],"computational":[51],"methods":[52],"predict":[54],"conformational":[56,102,150],"compounds":[59,81,109],"are":[60,184],"required":[61],"design":[63],"highly":[64,191],"selective":[65,192],"inhibitors.":[67,194],"In":[68],"this":[69],"study,":[70],"we":[71,131],"performed":[72,132],"absolute":[73],"binding":[74,93,160],"free-energy":[75],"perturbation":[76],"(ABFEP)":[77],"simulations":[78],"11":[80,108],"on":[82,173],"both":[83],"forms":[87],"ITK,":[89],"calculated":[92],"free":[94],"energies":[95],"were":[96,161],"compared":[97],"with":[98],"experimental":[99],"data.":[100],"The":[101,178],"10":[105],"was":[110],"correctly":[111],"predicted":[112],"using":[113],"ABFEP.":[114],"To":[115],"investigate":[116],"mechanism":[118],"underlying":[119],"stabilization":[121,143],"structures":[127],"by":[128],"compounds,":[130],"extensive,":[133],"conventional":[134],"molecular":[135],"dynamics":[136],"simulations,":[137],"which":[138],"revealed":[139],"compound-induced":[142],"P-loop":[146],"linkage":[148],"changes":[151],"in":[152],"L489,":[153],"V419,":[154],"F501,":[155],"M410":[157],"upon":[158],"compound":[159],"critical":[162],"factors.":[163,177],"A":[164],"guideline":[165],"designing":[167],"inactive-form":[168],"binders":[169],"proposed":[171],"based":[172],"these":[174],"key":[175],"structural":[176],"ABFEP":[179],"created":[182],"guidelines":[183],"expected":[185],"facilitate":[187],"discovery":[189]},"counts_by_year":[{"year":2026,"cited_by_count":4},{"year":2025,"cited_by_count":2},{"year":2024,"cited_by_count":3}],"updated_date":"2026-06-15T08:34:33.830935","created_date":"2025-10-10T00:00:00"}