{"id":"https://openalex.org/W4313236875","doi":"https://doi.org/10.1021/acs.jcim.2c01097","title":"Free-Energy Profiles for Membrane Permeation of Compounds Calculated Using Rare-Event Sampling Methods","display_name":"Free-Energy Profiles for Membrane Permeation of Compounds Calculated Using Rare-Event Sampling Methods","publication_year":2022,"publication_date":"2022-12-27","ids":{"openalex":"https://openalex.org/W4313236875","doi":"https://doi.org/10.1021/acs.jcim.2c01097","pmid":"https://pubmed.ncbi.nlm.nih.gov/36574612"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.2c01097","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.2c01097","pdf_url":null,"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":null,"license_id":null,"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":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5034873036","display_name":"Ryuhei Harada","orcid":"https://orcid.org/0000-0001-7987-0540"},"institutions":[{"id":"https://openalex.org/I146399215","display_name":"University of Tsukuba","ror":"https://ror.org/02956yf07","country_code":"JP","type":"education","lineage":["https://openalex.org/I146399215"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Ryuhei Harada","raw_affiliation_strings":["Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki305-8577, Japan"],"raw_orcid":"https://orcid.org/0000-0001-7987-0540","affiliations":[{"raw_affiliation_string":"Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki305-8577, Japan","institution_ids":["https://openalex.org/I146399215"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054539747","display_name":"Rikuri Morita","orcid":"https://orcid.org/0000-0002-0465-5528"},"institutions":[{"id":"https://openalex.org/I146399215","display_name":"University of Tsukuba","ror":"https://ror.org/02956yf07","country_code":"JP","type":"education","lineage":["https://openalex.org/I146399215"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Rikuri Morita","raw_affiliation_strings":["Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki305-8577, Japan"],"raw_orcid":"https://orcid.org/0000-0002-0465-5528","affiliations":[{"raw_affiliation_string":"Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki305-8577, Japan","institution_ids":["https://openalex.org/I146399215"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5048994262","display_name":"Yasuteru Shigeta","orcid":"https://orcid.org/0000-0002-3219-6007"},"institutions":[{"id":"https://openalex.org/I146399215","display_name":"University of Tsukuba","ror":"https://ror.org/02956yf07","country_code":"JP","type":"education","lineage":["https://openalex.org/I146399215"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Yasuteru Shigeta","raw_affiliation_strings":["Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki305-8577, Japan"],"raw_orcid":"https://orcid.org/0000-0002-3219-6007","affiliations":[{"raw_affiliation_string":"Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki305-8577, Japan","institution_ids":["https://openalex.org/I146399215"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5034873036"],"corresponding_institution_ids":["https://openalex.org/I146399215"],"apc_list":null,"apc_paid":null,"fwci":1.3325,"has_fulltext":false,"cited_by_count":21,"citation_normalized_percentile":{"value":0.8036006,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"63","issue":"1","first_page":"259","last_page":"269"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10432","display_name":"DNA and Nucleic Acid Chemistry","score":0.9994999766349792,"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/T10432","display_name":"DNA and Nucleic Acid Chemistry","score":0.9994999766349792,"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/T10044","display_name":"Protein Structure and Dynamics","score":0.9846000075340271,"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/T11177","display_name":"Spectroscopy and Quantum Chemical Studies","score":0.9836999773979187,"subfield":{"id":"https://openalex.org/subfields/3107","display_name":"Atomic and Molecular Physics, and Optics"},"field":{"id":"https://openalex.org/fields/31","display_name":"Physics and Astronomy"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/permeation","display_name":"Permeation","score":0.8524911403656006},{"id":"https://openalex.org/keywords/umbrella-sampling","display_name":"Umbrella sampling","score":0.8496827483177185},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.6734136343002319},{"id":"https://openalex.org/keywords/membrane","display_name":"Membrane","score":0.6478577852249146},{"id":"https://openalex.org/keywords/rare-events","display_name":"Rare events","score":0.604137122631073},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.5824509263038635},{"id":"https://openalex.org/keywords/metadynamics","display_name":"Metadynamics","score":0.521434485912323},{"id":"https://openalex.org/keywords/sampling","display_name":"Sampling (signal processing)","score":0.43059271574020386},{"id":"https://openalex.org/keywords/biological-system","display_name":"Biological system","score":0.39673811197280884},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.313901424407959},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.28919070959091187},{"id":"https://openalex.org/keywords/mathematics","display_name":"Mathematics","score":0.1116642951965332},{"id":"https://openalex.org/keywords/statistics","display_name":"Statistics","score":0.09904122352600098}],"concepts":[{"id":"https://openalex.org/C50670333","wikidata":"https://www.wikidata.org/wiki/Q907651","display_name":"Permeation","level":3,"score":0.8524911403656006},{"id":"https://openalex.org/C128747166","wikidata":"https://www.wikidata.org/wiki/Q7881414","display_name":"Umbrella sampling","level":3,"score":0.8496827483177185},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.6734136343002319},{"id":"https://openalex.org/C41625074","wikidata":"https://www.wikidata.org/wiki/Q176088","display_name":"Membrane","level":2,"score":0.6478577852249146},{"id":"https://openalex.org/C2777317252","wikidata":"https://www.wikidata.org/wiki/Q18393516","display_name":"Rare events","level":2,"score":0.604137122631073},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5824509263038635},{"id":"https://openalex.org/C62752575","wikidata":"https://www.wikidata.org/wiki/Q6822487","display_name":"Metadynamics","level":3,"score":0.521434485912323},{"id":"https://openalex.org/C140779682","wikidata":"https://www.wikidata.org/wiki/Q210868","display_name":"Sampling (signal processing)","level":3,"score":0.43059271574020386},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.39673811197280884},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.313901424407959},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.28919070959091187},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.1116642951965332},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.09904122352600098},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0},{"id":"https://openalex.org/C31972630","wikidata":"https://www.wikidata.org/wiki/Q844240","display_name":"Computer vision","level":1,"score":0.0},{"id":"https://openalex.org/C106131492","wikidata":"https://www.wikidata.org/wiki/Q3072260","display_name":"Filter (signal processing)","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D002463","descriptor_name":"Cell Membrane Permeability","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002463","descriptor_name":"Cell Membrane Permeability","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002463","descriptor_name":"Cell Membrane Permeability","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":"D011487","descriptor_name":"Protein Conformation","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":"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":2,"locations":[{"id":"doi:10.1021/acs.jcim.2c01097","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.2c01097","pdf_url":null,"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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:36574612","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/36574612","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}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Affordable and clean energy","score":0.8799999952316284,"id":"https://metadata.un.org/sdg/7"}],"awards":[{"id":"https://openalex.org/G7560602839","display_name":null,"funder_award_id":"JP21K06094","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G8113086940","display_name":null,"funder_award_id":"21K06094","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"}],"funders":[{"id":"https://openalex.org/F4320310657","display_name":"Sumitomo Foundation","ror":"https://ror.org/01nmpj461"},{"id":"https://openalex.org/F4320334764","display_name":"Japan Society for the Promotion of Science","ror":"https://ror.org/00hhkn466"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":83,"referenced_works":["https://openalex.org/W1917632116","https://openalex.org/W1963739311","https://openalex.org/W1974072532","https://openalex.org/W1974373394","https://openalex.org/W1974837363","https://openalex.org/W1976499671","https://openalex.org/W1984877105","https://openalex.org/W1986299453","https://openalex.org/W1993177346","https://openalex.org/W1995907662","https://openalex.org/W1997108831","https://openalex.org/W1999061920","https://openalex.org/W2001493784","https://openalex.org/W2015504080","https://openalex.org/W2016033647","https://openalex.org/W2021125439","https://openalex.org/W2021520922","https://openalex.org/W2023472866","https://openalex.org/W2025625972","https://openalex.org/W2034001167","https://openalex.org/W2035687084","https://openalex.org/W2036441926","https://openalex.org/W2038572295","https://openalex.org/W2040809566","https://openalex.org/W2045482407","https://openalex.org/W2051039246","https://openalex.org/W2051455807","https://openalex.org/W2053081979","https://openalex.org/W2055718543","https://openalex.org/W2057477511","https://openalex.org/W2057806291","https://openalex.org/W2064556178","https://openalex.org/W2065281489","https://openalex.org/W2065601090","https://openalex.org/W2066951434","https://openalex.org/W2068130700","https://openalex.org/W2068756855","https://openalex.org/W2074140794","https://openalex.org/W2075826312","https://openalex.org/W2080076400","https://openalex.org/W2081693079","https://openalex.org/W2096051522","https://openalex.org/W2103945336","https://openalex.org/W2128572087","https://openalex.org/W2154756937","https://openalex.org/W2160723824","https://openalex.org/W2164846849","https://openalex.org/W2262786960","https://openalex.org/W2320042080","https://openalex.org/W2323104785","https://openalex.org/W2323266363","https://openalex.org/W2331215510","https://openalex.org/W2339460745","https://openalex.org/W2465303803","https://openalex.org/W2516776474","https://openalex.org/W2518941287","https://openalex.org/W2520115971","https://openalex.org/W2527303815","https://openalex.org/W2560713311","https://openalex.org/W2564974142","https://openalex.org/W2569093964","https://openalex.org/W2570644968","https://openalex.org/W2580969766","https://openalex.org/W2590470445","https://openalex.org/W2595909561","https://openalex.org/W2605297867","https://openalex.org/W2736423475","https://openalex.org/W2751415108","https://openalex.org/W2777235740","https://openalex.org/W2784785876","https://openalex.org/W2886781218","https://openalex.org/W2892865232","https://openalex.org/W2900345897","https://openalex.org/W2901315612","https://openalex.org/W2911593691","https://openalex.org/W2953485655","https://openalex.org/W2969604201","https://openalex.org/W3014064183","https://openalex.org/W3042889538","https://openalex.org/W3048462249","https://openalex.org/W3177545261","https://openalex.org/W4245676270","https://openalex.org/W4294287432"],"related_works":["https://openalex.org/W2946273544","https://openalex.org/W2331758362","https://openalex.org/W2952262944","https://openalex.org/W1563927246","https://openalex.org/W4301359208","https://openalex.org/W2777625898","https://openalex.org/W2211343430","https://openalex.org/W3010863162","https://openalex.org/W2750551255","https://openalex.org/W3131999517"],"abstract_inverted_index":{"The":[0],"free-energy":[1,28,65,99,186,273,324],"profile":[2,29,274],"of":[3,18,53,101,146,188,239,283,330],"a":[4,69,95,102,121,198,223,240,258],"compound":[5,103],"is":[6],"an":[7,57,63],"essential":[8],"measurement":[9],"in":[10,46],"evaluating":[11],"the":[12,27,50,82,105,132,144,154,185,230,243,248,253,263,279,288,297,304,317,323,331],"membrane":[13,38,83,106,133,170,194,236,280,293,327],"permeation":[14,39,84,107,134,171,195,237],"process":[15,108],"by":[16,116,286],"means":[17],"theoretical":[19],"methods.":[20],"Computationally,":[21],"molecular":[22],"dynamics":[23],"(MD)":[24],"simulation":[25],"allows":[26],"calculation.":[30],"However,":[31],"MD":[32,179,213],"simulations":[33],"frequently":[34],"fail":[35],"to":[36,56,61,88,130,161,267],"sample":[37],"because":[40],"they":[41],"are":[42],"rare":[43],"events":[44],"induced":[45],"longer":[47],"timescales":[48],"than":[49],"accessible":[51],"timescale":[52],"MD,":[54],"leading":[55],"insufficient":[58],"conformational":[59,71,151,200,250,260,319],"search":[60,169,201,320],"calculate":[62],"incorrect":[64],"profile.":[66],"To":[67],"achieve":[68],"sufficient":[70],"search,":[72],"several":[73],"enhanced":[74,90,155],"sampling":[75,91,113,156,205],"methods":[76,114,119,141,157,167],"have":[77,120],"been":[78],"developed":[79,115],"and":[80,127,149,215,326],"elucidated":[81],"process.":[85,135],"In":[86,229,242,295],"addition":[87],"these":[89],"methods,":[92,206],"we":[93,183,277],"proposed":[94],"simple":[96,174],"yet":[97],"powerful":[98],"calculation":[100],"for":[104,192,257,291],"based":[109,196],"on":[110,124,137,197],"originally":[111],"rare-event":[112,204],"us.":[117],"Our":[118],"weak":[122],"dependency":[123],"external":[125,163],"biases":[126],"their":[128,150,193,292],"optimizations":[129],"promote":[131],"Based":[136],"distributed":[138],"computing,":[139],"our":[140,166],"only":[142],"require":[143],"selection":[145,212],"initial":[147,235,254],"structures":[148],"resampling,":[152],"whereas":[153],"may":[158],"be":[159],"required":[160],"adjust":[162],"biases.":[164],"Furthermore,":[165,276],"efficiently":[168],"processes":[172],"with":[173,222,303],"scripts":[175],"without":[176],"modifying":[177],"any":[178],"program.":[180],"As":[181],"demonstrations,":[182],"calculated":[184,298,322],"profiles":[187,325],"seven":[189,332],"linear":[190],"compounds":[191,285],"hybrid":[199,318],"using":[202],"two":[203],"that":[207,316],"is,":[208],"(1)":[209],"parallel":[210],"cascade":[211],"(PaCS-MD)":[214],"(2)":[216],"outlier":[217],"flooding":[218],"method":[219],"(OFLOOD),":[220],"combined":[221],"Markov":[224],"state":[225],"model":[226],"(MSM)":[227],"construction.":[228],"first":[231],"step,":[232,245],"PaCS-MD":[233],"generated":[234],"paths":[238],"compound.":[241],"second":[244],"OFLOOD":[246],"expanded":[247],"unsearched":[249],"area":[251],"around":[252],"paths,":[255],"allowing":[256],"broad":[259],"search.":[261],"Finally,":[262],"trajectories":[264],"were":[265,300],"employed":[266],"construct":[268],"reliable":[269,289],"MSMs,":[270],"enabling":[271],"correct":[272],"calculations.":[275],"estimated":[278],"permeability":[281,328],"coefficients":[282,299,329],"all":[284],"constructing":[287],"MSMs":[290],"permeation.":[294],"conclusion,":[296],"qualitatively":[301],"correlated":[302],"experimental":[305],"measurements":[306],"(correlation":[307],"coefficient":[308],"(":[309],"R":[310],"2":[311],")":[312],"=":[313],"0.8689),":[314],"indicating":[315],"successfully":[321],"compounds.":[333]},"counts_by_year":[{"year":2026,"cited_by_count":4},{"year":2025,"cited_by_count":7},{"year":2024,"cited_by_count":8},{"year":2023,"cited_by_count":1},{"year":2022,"cited_by_count":1}],"updated_date":"2026-07-30T17:31:21.811387","created_date":"2025-10-10T00:00:00"}
