{"id":"https://openalex.org/W2908766165","doi":"https://doi.org/10.1021/acs.jcim.8b00826","title":"Assessing the Predictive Power of Relative Binding Free Energy Calculations for Test Cases Involving Displacement of Binding Site Water Molecules","display_name":"Assessing the Predictive Power of Relative Binding Free Energy Calculations for Test Cases Involving Displacement of Binding Site Water Molecules","publication_year":2019,"publication_date":"2019-01-14","ids":{"openalex":"https://openalex.org/W2908766165","doi":"https://doi.org/10.1021/acs.jcim.8b00826","mag":"2908766165","pmid":"https://pubmed.ncbi.nlm.nih.gov/30640456"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.8b00826","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.8b00826","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":"publisher-specific-oa","license_id":"https://openalex.org/licenses/publisher-specific-oa","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/A5102723237","display_name":"Jo\u00ebl Wahl","orcid":"https://orcid.org/0000-0002-7904-9637"},"institutions":[{"id":"https://openalex.org/I1850255","display_name":"University of Basel","ror":"https://ror.org/02s6k3f65","country_code":"CH","type":"education","lineage":["https://openalex.org/I1850255"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Joel Wahl","raw_affiliation_strings":["Molecular Modeling, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Molecular Modeling, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland","institution_ids":["https://openalex.org/I1850255"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5058642572","display_name":"Martin Smie\u0161ko","orcid":"https://orcid.org/0000-0003-2758-2680"},"institutions":[{"id":"https://openalex.org/I1850255","display_name":"University of Basel","ror":"https://ror.org/02s6k3f65","country_code":"CH","type":"education","lineage":["https://openalex.org/I1850255"]}],"countries":["CH"],"is_corresponding":true,"raw_author_name":"Martin Smie\u0161ko","raw_affiliation_strings":["Molecular Modeling, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland"],"raw_orcid":"https://orcid.org/0000-0003-2758-2680","affiliations":[{"raw_affiliation_string":"Molecular Modeling, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland","institution_ids":["https://openalex.org/I1850255"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5058642572"],"corresponding_institution_ids":["https://openalex.org/I1850255"],"apc_list":null,"apc_paid":null,"fwci":2.4909,"has_fulltext":false,"cited_by_count":45,"citation_normalized_percentile":{"value":0.89884628,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":96,"max":99},"biblio":{"volume":"59","issue":"2","first_page":"754","last_page":"765"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9998999834060669,"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":0.9998999834060669,"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":0.9993000030517578,"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"}},{"id":"https://openalex.org/T10432","display_name":"DNA and Nucleic Acid Chemistry","score":0.9987000226974487,"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/solvation","display_name":"Solvation","score":0.773065984249115},{"id":"https://openalex.org/keywords/binding-energy","display_name":"Binding energy","score":0.6620417237281799},{"id":"https://openalex.org/keywords/free-energy-perturbation","display_name":"Free energy perturbation","score":0.5160391330718994},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.5070290565490723},{"id":"https://openalex.org/keywords/monte-carlo-method","display_name":"Monte Carlo method","score":0.5068309903144836},{"id":"https://openalex.org/keywords/molecule","display_name":"Molecule","score":0.4924655854701996},{"id":"https://openalex.org/keywords/statistical-physics","display_name":"Statistical physics","score":0.46021831035614014},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.4136753976345062},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.3475193977355957},{"id":"https://openalex.org/keywords/thermodynamics","display_name":"Thermodynamics","score":0.3420525789260864},{"id":"https://openalex.org/keywords/chemical-physics","display_name":"Chemical physics","score":0.3324553966522217},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.27386748790740967},{"id":"https://openalex.org/keywords/atomic-physics","display_name":"Atomic physics","score":0.1924341320991516},{"id":"https://openalex.org/keywords/mathematics","display_name":"Mathematics","score":0.10270941257476807}],"concepts":[{"id":"https://openalex.org/C148093993","wikidata":"https://www.wikidata.org/wiki/Q739398","display_name":"Solvation","level":3,"score":0.773065984249115},{"id":"https://openalex.org/C93282013","wikidata":"https://www.wikidata.org/wiki/Q420754","display_name":"Binding energy","level":2,"score":0.6620417237281799},{"id":"https://openalex.org/C162641036","wikidata":"https://www.wikidata.org/wiki/Q5500215","display_name":"Free energy perturbation","level":3,"score":0.5160391330718994},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5070290565490723},{"id":"https://openalex.org/C19499675","wikidata":"https://www.wikidata.org/wiki/Q232207","display_name":"Monte Carlo method","level":2,"score":0.5068309903144836},{"id":"https://openalex.org/C32909587","wikidata":"https://www.wikidata.org/wiki/Q11369","display_name":"Molecule","level":2,"score":0.4924655854701996},{"id":"https://openalex.org/C121864883","wikidata":"https://www.wikidata.org/wiki/Q677916","display_name":"Statistical physics","level":1,"score":0.46021831035614014},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.4136753976345062},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.3475193977355957},{"id":"https://openalex.org/C97355855","wikidata":"https://www.wikidata.org/wiki/Q11473","display_name":"Thermodynamics","level":1,"score":0.3420525789260864},{"id":"https://openalex.org/C159467904","wikidata":"https://www.wikidata.org/wiki/Q2001702","display_name":"Chemical physics","level":1,"score":0.3324553966522217},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.27386748790740967},{"id":"https://openalex.org/C184779094","wikidata":"https://www.wikidata.org/wiki/Q26383","display_name":"Atomic physics","level":1,"score":0.1924341320991516},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.10270941257476807},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.0},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","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":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","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":"D009010","descriptor_name":"Monte Carlo Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009010","descriptor_name":"Monte Carlo Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009010","descriptor_name":"Monte Carlo Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012997","descriptor_name":"Solvents","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D012997","descriptor_name":"Solvents","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D012997","descriptor_name":"Solvents","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.8b00826","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.8b00826","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":"publisher-specific-oa","license_id":"https://openalex.org/licenses/publisher-specific-oa","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:30640456","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/30640456","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:edoc.unibas.ch:70111","is_oa":false,"landing_page_url":"https://edoc.unibas.ch/70111/","pdf_url":null,"source":{"id":"https://openalex.org/S4306401836","display_name":"edoc (University of Basel)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1850255","host_organization_name":"University of Basel","host_organization_lineage":["https://openalex.org/I1850255"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Affordable and clean energy","id":"https://metadata.un.org/sdg/7","score":0.6499999761581421}],"awards":[{"id":"https://openalex.org/G2377225453","display_name":null,"funder_award_id":"200020_159952","funder_id":"https://openalex.org/F4320320924","funder_display_name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung"}],"funders":[{"id":"https://openalex.org/F4320320924","display_name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","ror":"https://ror.org/00yjd3n13"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":51,"referenced_works":["https://openalex.org/W1968904047","https://openalex.org/W1971652848","https://openalex.org/W1979315020","https://openalex.org/W1980138534","https://openalex.org/W1982440179","https://openalex.org/W1984481443","https://openalex.org/W1992921903","https://openalex.org/W1998948060","https://openalex.org/W2003984869","https://openalex.org/W2013173369","https://openalex.org/W2014433873","https://openalex.org/W2024726841","https://openalex.org/W2025161493","https://openalex.org/W2055648985","https://openalex.org/W2056640340","https://openalex.org/W2059832777","https://openalex.org/W2070753604","https://openalex.org/W2078391824","https://openalex.org/W2086190523","https://openalex.org/W2093327248","https://openalex.org/W2099282863","https://openalex.org/W2120987099","https://openalex.org/W2132629607","https://openalex.org/W2133641393","https://openalex.org/W2141715793","https://openalex.org/W2146942655","https://openalex.org/W2147993766","https://openalex.org/W2153228625","https://openalex.org/W2154670681","https://openalex.org/W2222589778","https://openalex.org/W2233260369","https://openalex.org/W2315679499","https://openalex.org/W2323942455","https://openalex.org/W2330936115","https://openalex.org/W2333104569","https://openalex.org/W2339113488","https://openalex.org/W2340488228","https://openalex.org/W2480023505","https://openalex.org/W2495180161","https://openalex.org/W2511847589","https://openalex.org/W2515097834","https://openalex.org/W2552522590","https://openalex.org/W2573266977","https://openalex.org/W2597025763","https://openalex.org/W2738131613","https://openalex.org/W2772606519","https://openalex.org/W2784827262","https://openalex.org/W2802312828","https://openalex.org/W2895277606","https://openalex.org/W2900735593","https://openalex.org/W2952635193"],"related_works":["https://openalex.org/W2067207114","https://openalex.org/W3175840220","https://openalex.org/W2049601662","https://openalex.org/W2237020303","https://openalex.org/W2089807142","https://openalex.org/W2050023963","https://openalex.org/W2116929165","https://openalex.org/W2036024373","https://openalex.org/W1978483079","https://openalex.org/W2024556718"],"abstract_inverted_index":{"Improved":[0],"sampling":[1,129],"methodologies,":[2],"more":[3],"accurate":[4],"force":[5],"fields,":[6],"and":[7,37,88,109],"access":[8],"to":[9,16,33,62,132,138,151],"longer":[10],"simulation":[11],"time":[12],"scales":[13],"have":[14],"led":[15,137],"an":[17],"increased":[18],"application":[19],"of":[20,39,74,82,154,157,168,177,191,199,207,222,225],"Relative":[21],"Binding":[22],"Free":[23,57],"Energy":[24,58],"(RBFE)":[25],"calculations":[26,61,215],"in":[27,51,71,79],"drug":[28],"discovery":[29],"projects.":[30],"In":[31],"order":[32],"assess":[34],"the":[35,49,69,80,90,97,102,116,133,143,152,155,158,165,169,174,178,181,189,208,226,230],"strengths":[36],"limitations":[38],"such":[40],"tools,":[41],"adequate":[42],"benchmark":[43],"sets":[44],"are":[45,203],"required":[46],"that":[47,136,164,202,213],"challenge":[48],"methodology":[50],"certain":[52],"well-defined":[53],"aspects.":[54],"We":[55,100,119],"applied":[56,121],"Perturbation":[59],"(FEP)":[60],"six":[63],"congeneric":[64],"ligand":[65],"pairs":[66],"taken":[67],"from":[68,104,218],"literature,":[70],"which":[72],"addition":[73],"a":[75,122,139,147],"functional":[76],"group":[77],"resulted":[78],"displacement":[81],"buried":[83,200,223],"binding":[84,93,192,227],"site":[85,149,193],"water":[86,194],"molecules":[87,195],"compared":[89],"calculated":[91,117],"relative":[92],"free":[94],"energies":[95],"with":[96,229],"experimental":[98],"ones.":[99],"started":[101],"perturbations":[103],"different":[105],"initial":[106,183],"solvation":[107,198],"states":[108],"registered":[110],"large":[111],"inconsistencies":[112],"(large":[113],"hysteresis)":[114],"between":[115],"values.":[118],"furthermore":[120],"Grand":[123],"Canonical":[124],"Monte":[125],"Carlo":[126],"(GCMC)":[127],"solvent":[128,220],"step":[130],"prior":[131],"FEP":[134],"calculation":[135],"smaller":[140],"hysteresis":[141],"for":[142],"simulations.":[144],"By":[145],"applying":[146],"hydration":[148],"analysis":[150],"trajectories":[153],"end-states":[156],"perturbation,":[159],"we":[160],"could":[161],"point":[162],"out":[163],"low":[166],"accuracy":[167],"predictions":[170],"as":[171,173],"well":[172],"high":[175],"dependence":[176],"prediction":[179],"on":[180],"chosen":[182],"state":[184],"is":[185],"likely":[186],"caused":[187],"by":[188],"trapping":[190],"and/or":[196],"insufficient":[197],"cavities":[201],"formed":[204],"upon":[205],"completion":[206],"perturbation.":[209],"This":[210],"work":[211],"highlights":[212],"RBFE":[214],"can":[216],"suffer":[217],"slow":[219],"exchange":[221],"parts":[224],"sites":[228],"bulk.":[231]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":5},{"year":2024,"cited_by_count":3},{"year":2023,"cited_by_count":7},{"year":2022,"cited_by_count":9},{"year":2021,"cited_by_count":9},{"year":2020,"cited_by_count":8},{"year":2019,"cited_by_count":3}],"updated_date":"2025-11-06T03:46:38.306776","created_date":"2025-10-10T00:00:00"}