{"id":"https://openalex.org/W3109470511","doi":"https://doi.org/10.1021/acs.jcim.0c01133","title":"Advancing GIST-Based Solvent Functionals through Multiobjective Optimization of Solvent Enthalpy and Entropy Scoring Terms","display_name":"Advancing GIST-Based Solvent Functionals through Multiobjective Optimization of Solvent Enthalpy and Entropy Scoring Terms","publication_year":2020,"publication_date":"2020-12-02","ids":{"openalex":"https://openalex.org/W3109470511","doi":"https://doi.org/10.1021/acs.jcim.0c01133","mag":"3109470511","pmid":"https://pubmed.ncbi.nlm.nih.gov/33264016"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.0c01133","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.0c01133","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/A5087835830","display_name":"T. H\u00fcfner","orcid":"https://orcid.org/0000-0003-1457-3603"},"institutions":[{"id":"https://openalex.org/I161103922","display_name":"Philipps University of Marburg","ror":"https://ror.org/01rdrb571","country_code":"DE","type":"education","lineage":["https://openalex.org/I161103922"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Tobias H\u00fcfner-Wulsdorf","raw_affiliation_strings":["Institut f\u00fcr Pharmazeutische Chemie, Philipps Universit\u00e4t Marburg, Marbacher Weg 6, 35037 Marburg, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institut f\u00fcr Pharmazeutische Chemie, Philipps Universit\u00e4t Marburg, Marbacher Weg 6, 35037 Marburg, Germany","institution_ids":["https://openalex.org/I161103922"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5005420915","display_name":"G. Klebe","orcid":"https://orcid.org/0000-0002-4913-390X"},"institutions":[{"id":"https://openalex.org/I161103922","display_name":"Philipps University of Marburg","ror":"https://ror.org/01rdrb571","country_code":"DE","type":"education","lineage":["https://openalex.org/I161103922"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Gerhard Klebe","raw_affiliation_strings":["Institut f\u00fcr Pharmazeutische Chemie, Philipps Universit\u00e4t Marburg, Marbacher Weg 6, 35037 Marburg, Germany"],"raw_orcid":"https://orcid.org/0000-0002-4913-390X","affiliations":[{"raw_affiliation_string":"Institut f\u00fcr Pharmazeutische Chemie, Philipps Universit\u00e4t Marburg, Marbacher Weg 6, 35037 Marburg, Germany","institution_ids":["https://openalex.org/I161103922"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5005420915"],"corresponding_institution_ids":["https://openalex.org/I161103922"],"apc_list":null,"apc_paid":null,"fwci":0.7226,"has_fulltext":false,"cited_by_count":8,"citation_normalized_percentile":{"value":0.77731609,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":98},"biblio":{"volume":"60","issue":"12","first_page":"6654","last_page":"6665"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9991999864578247,"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/T13539","display_name":"thermodynamics and calorimetric analyses","score":0.9983999729156494,"subfield":{"id":"https://openalex.org/subfields/1606","display_name":"Physical and Theoretical Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/isothermal-titration-calorimetry","display_name":"Isothermal titration calorimetry","score":0.7253314256668091},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.6855865120887756},{"id":"https://openalex.org/keywords/enthalpy","display_name":"Enthalpy","score":0.6647335290908813},{"id":"https://openalex.org/keywords/thermodynamics","display_name":"Thermodynamics","score":0.5810310244560242},{"id":"https://openalex.org/keywords/solvent","display_name":"Solvent","score":0.5231075286865234},{"id":"https://openalex.org/keywords/molecule","display_name":"Molecule","score":0.5093561410903931},{"id":"https://openalex.org/keywords/solvation","display_name":"Solvation","score":0.5058879256248474},{"id":"https://openalex.org/keywords/ligand","display_name":"Ligand (biochemistry)","score":0.4952036440372467},{"id":"https://openalex.org/keywords/accessible-surface-area","display_name":"Accessible surface area","score":0.48774367570877075},{"id":"https://openalex.org/keywords/entropy","display_name":"Entropy (arrow of time)","score":0.483539342880249},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.46193185448646545},{"id":"https://openalex.org/keywords/protein-ligand","display_name":"Protein ligand","score":0.43618693947792053},{"id":"https://openalex.org/keywords/heat-capacity","display_name":"Heat capacity","score":0.4334317445755005},{"id":"https://openalex.org/keywords/physical-chemistry","display_name":"Physical chemistry","score":0.3504461646080017},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.10520219802856445},{"id":"https://openalex.org/keywords/organic-chemistry","display_name":"Organic chemistry","score":0.08959132432937622}],"concepts":[{"id":"https://openalex.org/C156911925","wikidata":"https://www.wikidata.org/wiki/Q643384","display_name":"Isothermal titration calorimetry","level":2,"score":0.7253314256668091},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6855865120887756},{"id":"https://openalex.org/C3288061","wikidata":"https://www.wikidata.org/wiki/Q161064","display_name":"Enthalpy","level":2,"score":0.6647335290908813},{"id":"https://openalex.org/C97355855","wikidata":"https://www.wikidata.org/wiki/Q11473","display_name":"Thermodynamics","level":1,"score":0.5810310244560242},{"id":"https://openalex.org/C2780471494","wikidata":"https://www.wikidata.org/wiki/Q146505","display_name":"Solvent","level":2,"score":0.5231075286865234},{"id":"https://openalex.org/C32909587","wikidata":"https://www.wikidata.org/wiki/Q11369","display_name":"Molecule","level":2,"score":0.5093561410903931},{"id":"https://openalex.org/C148093993","wikidata":"https://www.wikidata.org/wiki/Q739398","display_name":"Solvation","level":3,"score":0.5058879256248474},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.4952036440372467},{"id":"https://openalex.org/C11072593","wikidata":"https://www.wikidata.org/wiki/Q3622068","display_name":"Accessible surface area","level":2,"score":0.48774367570877075},{"id":"https://openalex.org/C106301342","wikidata":"https://www.wikidata.org/wiki/Q4117933","display_name":"Entropy (arrow of time)","level":2,"score":0.483539342880249},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.46193185448646545},{"id":"https://openalex.org/C109095088","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Protein ligand","level":2,"score":0.43618693947792053},{"id":"https://openalex.org/C60205243","wikidata":"https://www.wikidata.org/wiki/Q179388","display_name":"Heat capacity","level":2,"score":0.4334317445755005},{"id":"https://openalex.org/C147789679","wikidata":"https://www.wikidata.org/wiki/Q11372","display_name":"Physical chemistry","level":1,"score":0.3504461646080017},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.10520219802856445},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.08959132432937622},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D002151","descriptor_name":"Calorimetry","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002151","descriptor_name":"Calorimetry","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002151","descriptor_name":"Calorimetry","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":"D011485","descriptor_name":"Protein Binding","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":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012997","descriptor_name":"Solvents","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012997","descriptor_name":"Solvents","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012997","descriptor_name":"Solvents","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":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019277","descriptor_name":"Entropy","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D019277","descriptor_name":"Entropy","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D019277","descriptor_name":"Entropy","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.0c01133","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.0c01133","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:33264016","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/33264016","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":[{"score":0.8500000238418579,"id":"https://metadata.un.org/sdg/6","display_name":"Clean water and sanitation"}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":45,"referenced_works":["https://openalex.org/W255996521","https://openalex.org/W1967809254","https://openalex.org/W1971652848","https://openalex.org/W1976161355","https://openalex.org/W1979315020","https://openalex.org/W1992921903","https://openalex.org/W2004822259","https://openalex.org/W2005647584","https://openalex.org/W2011668781","https://openalex.org/W2015647581","https://openalex.org/W2017829285","https://openalex.org/W2032665736","https://openalex.org/W2041922739","https://openalex.org/W2050122005","https://openalex.org/W2064105358","https://openalex.org/W2081771891","https://openalex.org/W2086190523","https://openalex.org/W2095242270","https://openalex.org/W2103394918","https://openalex.org/W2106140689","https://openalex.org/W2107676206","https://openalex.org/W2114239896","https://openalex.org/W2122460390","https://openalex.org/W2126105956","https://openalex.org/W2149263899","https://openalex.org/W2313116527","https://openalex.org/W2330936115","https://openalex.org/W2332328354","https://openalex.org/W2332712348","https://openalex.org/W2404280981","https://openalex.org/W2421223463","https://openalex.org/W2473001210","https://openalex.org/W2552941407","https://openalex.org/W2577617335","https://openalex.org/W2741729445","https://openalex.org/W2793806514","https://openalex.org/W2802312828","https://openalex.org/W2808043637","https://openalex.org/W2885056890","https://openalex.org/W2908766165","https://openalex.org/W2909638144","https://openalex.org/W2913105929","https://openalex.org/W3000181972","https://openalex.org/W3005776600","https://openalex.org/W4239632189"],"related_works":["https://openalex.org/W2016222666","https://openalex.org/W1804028855","https://openalex.org/W1974433778","https://openalex.org/W2119839118","https://openalex.org/W2576615467","https://openalex.org/W1991995101","https://openalex.org/W1966793603","https://openalex.org/W2089700360","https://openalex.org/W2127533558","https://openalex.org/W1989868941"],"abstract_inverted_index":{"Water":[0],"molecules":[1,153,224],"and":[2,8,32,94,109,119,133,232,245],"their":[3],"impact":[4],"on":[5,154],"the":[6,29,58,62,66,70,81,91,99,112,116,120,142,151,155,158,168,176,194,200,235],"enthalpy":[7,31],"entropy":[9,33],"of":[10,14,36,51,57,83,90,111,123,157,175,203],"protein-ligand":[11,243],"binding":[12,72,117,146,208],"are":[13],"considerable":[15],"interest":[16],"in":[17,103,115,242],"drug":[18],"discovery.":[19],"In":[20],"this":[21],"contribution,":[22],"we":[23,171],"use":[24],"multiobjective":[25],"optimization":[26],"to":[27,44,69,77,80,207,218,222,228],"fit":[28],"solvent":[30,42,92,152],"scoring":[34,113],"terms":[35],"grid":[37],"inhomogeneous":[38],"solvation":[39],"theory":[40],"(GIST)-based":[41],"functionals":[43,93],"measured":[45,229,246],"isothermal":[46],"titration":[47],"calorimetry":[48],"(ITC)":[49],"data":[50,135],"protein-ligand-binding":[52],"reactions":[53],"for":[54,164,186,193],"ligand":[55,64,160],"pairs":[56],"protein":[59,181,189],"thrombin.":[60],"For":[61],"investigated":[63],"pairs,":[65],"overwhelming":[67],"contribution":[68,82],"relative":[71],"affinity":[73],"difference":[74],"is":[75,226],"assumed":[76],"be":[78],"attributed":[79],"water":[84,205,223,240],"molecules.":[85],"We":[86,126],"present":[87],"different":[88],"implementations":[89],"then":[95],"proceed":[96],"by":[97],"analyzing":[98],"most":[100],"successful":[101],"one":[102],"more":[104],"detail":[105],"through":[106,167,199],"error":[107],"assessment":[108],"presentation":[110],"regions":[114],"pocket":[118],"unbound":[121,159],"ligands":[122],"selected":[124],"examples.":[125],"find":[127,172],"overall":[128,211],"good":[129],"agreement":[130],"between":[131,179,237],"calculated":[132],"experimental":[134],"and,":[136],"although":[137],"physically":[138],"not":[139],"fully":[140],"justified,":[141],"ligand-desolvation":[143],"score":[144],"increases":[145],"affinity,":[147],"thus":[148,183],"suggesting":[149,184],"that":[150,225],"surface":[156],"constitute":[161],"a":[162,215],"proxy":[163],"interactions":[165],"gained":[166],"protein.":[169],"Furthermore,":[170],"limited":[173,195],"transferability":[174,196],"parameters":[177],"even":[178],"similar":[180],"targets,":[182],"refitting":[185],"each":[187],"new":[188],"target.":[190],"Possible":[191],"reasons":[192],"may":[197],"arise":[198],"initial":[201],"assumption":[202],"dominating":[204],"contributions":[206],"affinity.":[209],"Nonetheless,":[210],"our":[212],"study":[213],"demonstrates":[214],"consistent":[216],"approach":[217],"assign":[219],"thermodynamic":[220,230,247],"quantities":[221],"sensible":[227],"signatures":[231],"enables":[233],"bridging":[234],"gap":[236],"experimentally":[238],"determined":[239],"positions":[241],"complexes":[244],"data.":[248]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":1},{"year":2022,"cited_by_count":3},{"year":2021,"cited_by_count":1}],"updated_date":"2026-03-27T05:58:40.876381","created_date":"2025-10-10T00:00:00"}
