{"id":"https://openalex.org/W4324132700","doi":"https://doi.org/10.1021/acs.jcim.2c01610","title":"Accounting for Solvation Correlation Effects on the Thermodynamics of Water Networks in Protein Cavities","display_name":"Accounting for Solvation Correlation Effects on the Thermodynamics of Water Networks in Protein Cavities","publication_year":2023,"publication_date":"2023-03-14","ids":{"openalex":"https://openalex.org/W4324132700","doi":"https://doi.org/10.1021/acs.jcim.2c01610","pmid":"https://pubmed.ncbi.nlm.nih.gov/36917685"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.2c01610","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.2c01610","pdf_url":"https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.2c01610","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","license_id":"https://openalex.org/licenses/cc-by","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.2c01610","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5058218127","display_name":"Em\u00edlia P. Barros","orcid":"https://orcid.org/0000-0001-9755-260X"},"institutions":[{"id":"https://openalex.org/I35440088","display_name":"ETH Zurich","ror":"https://ror.org/05a28rw58","country_code":"CH","type":"education","lineage":["https://openalex.org/I2799323385","https://openalex.org/I35440088"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Emilia P. Barros","raw_affiliation_strings":["Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, Vladimir-Prelog-Weg 2, 8093 Z\u00fcrich, Switzerland"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, Vladimir-Prelog-Weg 2, 8093 Z\u00fcrich, Switzerland","institution_ids":["https://openalex.org/I35440088"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082893610","display_name":"Benjamin Ries","orcid":"https://orcid.org/0000-0002-0945-8304"},"institutions":[{"id":"https://openalex.org/I35440088","display_name":"ETH Zurich","ror":"https://ror.org/05a28rw58","country_code":"CH","type":"education","lineage":["https://openalex.org/I2799323385","https://openalex.org/I35440088"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Benjamin Ries","raw_affiliation_strings":["Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, Vladimir-Prelog-Weg 2, 8093 Z\u00fcrich, Switzerland"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, Vladimir-Prelog-Weg 2, 8093 Z\u00fcrich, Switzerland","institution_ids":["https://openalex.org/I35440088"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029568273","display_name":"Candide Champion","orcid":"https://orcid.org/0000-0001-6982-1569"},"institutions":[{"id":"https://openalex.org/I35440088","display_name":"ETH Zurich","ror":"https://ror.org/05a28rw58","country_code":"CH","type":"education","lineage":["https://openalex.org/I2799323385","https://openalex.org/I35440088"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Candide Champion","raw_affiliation_strings":["Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, Vladimir-Prelog-Weg 2, 8093 Z\u00fcrich, Switzerland"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, Vladimir-Prelog-Weg 2, 8093 Z\u00fcrich, Switzerland","institution_ids":["https://openalex.org/I35440088"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042555338","display_name":"Salom\u00e9 R. Rieder","orcid":"https://orcid.org/0000-0001-8036-651X"},"institutions":[{"id":"https://openalex.org/I35440088","display_name":"ETH Zurich","ror":"https://ror.org/05a28rw58","country_code":"CH","type":"education","lineage":["https://openalex.org/I2799323385","https://openalex.org/I35440088"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Salom\u00e9 R. Rieder","raw_affiliation_strings":["Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, Vladimir-Prelog-Weg 2, 8093 Z\u00fcrich, Switzerland"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, Vladimir-Prelog-Weg 2, 8093 Z\u00fcrich, Switzerland","institution_ids":["https://openalex.org/I35440088"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5019754904","display_name":"Sereina Riniker","orcid":"https://orcid.org/0000-0003-1893-4031"},"institutions":[{"id":"https://openalex.org/I35440088","display_name":"ETH Zurich","ror":"https://ror.org/05a28rw58","country_code":"CH","type":"education","lineage":["https://openalex.org/I2799323385","https://openalex.org/I35440088"]}],"countries":["CH"],"is_corresponding":true,"raw_author_name":"Sereina Riniker","raw_affiliation_strings":["Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, Vladimir-Prelog-Weg 2, 8093 Z\u00fcrich, Switzerland"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, Vladimir-Prelog-Weg 2, 8093 Z\u00fcrich, Switzerland","institution_ids":["https://openalex.org/I35440088"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5019754904"],"corresponding_institution_ids":["https://openalex.org/I35440088"],"apc_list":null,"apc_paid":null,"fwci":1.8472,"has_fulltext":true,"cited_by_count":12,"citation_normalized_percentile":{"value":0.84986194,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":97,"max":98},"biblio":{"volume":"63","issue":"6","first_page":"1794","last_page":"1805"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.9995999932289124,"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/T12534","display_name":"Protein Degradation and Inhibitors","score":0.9995999932289124,"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/T11178","display_name":"Receptor Mechanisms and Signaling","score":0.9958999752998352,"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":0.9952999949455261,"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":0.9111260175704956},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.6503685712814331},{"id":"https://openalex.org/keywords/implicit-solvation","display_name":"Implicit solvation","score":0.5786914229393005},{"id":"https://openalex.org/keywords/water-model","display_name":"Water model","score":0.4481215476989746},{"id":"https://openalex.org/keywords/drug-discovery","display_name":"Drug discovery","score":0.42576470971107483},{"id":"https://openalex.org/keywords/protein-ligand","display_name":"Protein ligand","score":0.4228728115558624},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.3462426960468292},{"id":"https://openalex.org/keywords/thermodynamics","display_name":"Thermodynamics","score":0.33901873230934143},{"id":"https://openalex.org/keywords/molecule","display_name":"Molecule","score":0.3364911675453186},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.3206164836883545},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.18361034989356995}],"concepts":[{"id":"https://openalex.org/C148093993","wikidata":"https://www.wikidata.org/wiki/Q739398","display_name":"Solvation","level":3,"score":0.9111260175704956},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6503685712814331},{"id":"https://openalex.org/C64147673","wikidata":"https://www.wikidata.org/wiki/Q6007318","display_name":"Implicit solvation","level":4,"score":0.5786914229393005},{"id":"https://openalex.org/C119049451","wikidata":"https://www.wikidata.org/wiki/Q3318070","display_name":"Water model","level":3,"score":0.4481215476989746},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.42576470971107483},{"id":"https://openalex.org/C109095088","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Protein ligand","level":2,"score":0.4228728115558624},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.3462426960468292},{"id":"https://openalex.org/C97355855","wikidata":"https://www.wikidata.org/wiki/Q11473","display_name":"Thermodynamics","level":1,"score":0.33901873230934143},{"id":"https://openalex.org/C32909587","wikidata":"https://www.wikidata.org/wiki/Q11369","display_name":"Molecule","level":2,"score":0.3364911675453186},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.3206164836883545},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.18361034989356995},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"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":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002417","descriptor_name":"Cattle","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002417","descriptor_name":"Cattle","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002417","descriptor_name":"Cattle","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":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D011506","descriptor_name":"Proteins","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":"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":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D014867","descriptor_name":"Water","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.2c01610","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.2c01610","pdf_url":"https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.2c01610","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","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:36917685","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/36917685","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:10052353","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10052353","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10052353/pdf/ci2c01610.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","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.2c01610","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.2c01610","pdf_url":"https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.2c01610","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","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Clean water and sanitation","id":"https://metadata.un.org/sdg/6","score":0.8299999833106995}],"awards":[],"funders":[{"id":"https://openalex.org/F4320321652","display_name":"Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich","ror":"https://ror.org/05a28rw58"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4324132700.pdf","grobid_xml":"https://content.openalex.org/works/W4324132700.grobid-xml"},"referenced_works_count":81,"referenced_works":["https://openalex.org/W1625910593","https://openalex.org/W1965009739","https://openalex.org/W1971556338","https://openalex.org/W1983066351","https://openalex.org/W1984690321","https://openalex.org/W1987161922","https://openalex.org/W1992921903","https://openalex.org/W1998948060","https://openalex.org/W2012500759","https://openalex.org/W2014433873","https://openalex.org/W2015647379","https://openalex.org/W2023095911","https://openalex.org/W2023222460","https://openalex.org/W2051612998","https://openalex.org/W2053381695","https://openalex.org/W2057572513","https://openalex.org/W2058698413","https://openalex.org/W2065009334","https://openalex.org/W2068307544","https://openalex.org/W2077096083","https://openalex.org/W2077790273","https://openalex.org/W2081719547","https://openalex.org/W2086308487","https://openalex.org/W2105880941","https://openalex.org/W2107676206","https://openalex.org/W2123162087","https://openalex.org/W2123647733","https://openalex.org/W2145991947","https://openalex.org/W2158272796","https://openalex.org/W2162027701","https://openalex.org/W2163430576","https://openalex.org/W2228949267","https://openalex.org/W2261819980","https://openalex.org/W2333639487","https://openalex.org/W2399386526","https://openalex.org/W2404861930","https://openalex.org/W2421223463","https://openalex.org/W2473001210","https://openalex.org/W2535858809","https://openalex.org/W2609454166","https://openalex.org/W2611735159","https://openalex.org/W2614931299","https://openalex.org/W2743935521","https://openalex.org/W2748795079","https://openalex.org/W2756885549","https://openalex.org/W2765889348","https://openalex.org/W2766288270","https://openalex.org/W2794400040","https://openalex.org/W2803653576","https://openalex.org/W2885056890","https://openalex.org/W2889287654","https://openalex.org/W2889351965","https://openalex.org/W2892851404","https://openalex.org/W2898871784","https://openalex.org/W2908766165","https://openalex.org/W2921674955","https://openalex.org/W2967496768","https://openalex.org/W2970854154","https://openalex.org/W2972491973","https://openalex.org/W2972636244","https://openalex.org/W3011089475","https://openalex.org/W3014682240","https://openalex.org/W3018000560","https://openalex.org/W3018950211","https://openalex.org/W3027827456","https://openalex.org/W3040072668","https://openalex.org/W3047663514","https://openalex.org/W3054319032","https://openalex.org/W3080868448","https://openalex.org/W3087002443","https://openalex.org/W3087130502","https://openalex.org/W3087352249","https://openalex.org/W3088183071","https://openalex.org/W3108360383","https://openalex.org/W3111206976","https://openalex.org/W3131446155","https://openalex.org/W4205322734","https://openalex.org/W4211166631","https://openalex.org/W4280629028","https://openalex.org/W4281741016","https://openalex.org/W4293298786"],"related_works":["https://openalex.org/W1966793603","https://openalex.org/W2048341727","https://openalex.org/W2089507369","https://openalex.org/W2045242973","https://openalex.org/W1974433778","https://openalex.org/W2498829061","https://openalex.org/W2053689559","https://openalex.org/W4323037679","https://openalex.org/W2062824236","https://openalex.org/W2120347752"],"abstract_inverted_index":{"Macromolecular":[0],"recognition":[1],"and":[2,12,39,70,98,151,164,202,232,243],"ligand":[3,241],"binding":[4,45,134,242],"are":[5,51],"at":[6],"the":[7,24,32,37,41,44,91,122,137,140,158,168,172,182,187,196,199,203,207],"core":[8],"of":[9,43,58,93,105,107,125,129,139,167,174,184,186,198,209,237],"biological":[10],"function":[11],"drug":[13,76,226],"discovery":[14,77,227],"efforts.":[15],"Water":[16],"molecules":[17,131],"play":[18],"a":[19,56,230],"significant":[20],"role":[21],"in":[22,67,113,132,212],"mediating":[23],"protein-ligand":[25],"interaction,":[26],"acting":[27],"as":[28],"more":[29],"than":[30],"just":[31],"surrounding":[33],"medium":[34],"by":[35,190,228],"affecting":[36],"thermodynamics":[38],"thus":[40],"outcome":[42],"process.":[46],"As":[47],"individual":[48],"water":[49,95,108,130,179,188,200,210],"contributions":[50,74],"impossible":[52],"to":[53,63],"measure":[54],"experimentally,":[55],"range":[57],"computational":[59],"methods":[60,82],"have":[61],"emerged":[62],"identify":[64],"hydration":[65],"sites":[66,96,189],"protein":[68,133,215],"pockets":[69,135],"characterize":[71],"their":[72],"energetic":[73],"for":[75,224],"applications.":[78],"Even":[79],"though":[80],"several":[81],"model":[83],"solvation":[84,100,175,238],"effects":[85,102,124,177,239],"explicitly,":[86],"they":[87],"focus":[88],"on":[89,157,178,195,240],"determining":[90],"stability":[92],"specific":[94],"independently":[97],"neglect":[99],"correlation":[101,176],"upon":[103],"replacement":[104,185],"clusters":[106],"molecules,":[109],"which":[110,145],"typically":[111],"happens":[112],"hit-to-lead":[114],"optimization.":[115],"In":[116],"this":[117],"work,":[118],"we":[119,217],"rigorously":[120],"determine":[121],"conjoint":[123],"replacing":[126],"all":[127],"combinations":[128],"through":[136],"use":[138],"RE-EDS":[141],"multistate":[142],"free-energy":[143],"method,":[144],"combines":[146],"Hamiltonian":[147],"replica":[148],"exchange":[149],"(RE)":[150],"enveloping":[152],"distribution":[153],"sampling":[154],"(EDS).":[155],"Applications":[156],"small":[159],"bovine":[160],"pancreatic":[161],"trypsin":[162],"inhibitor":[163],"four":[165],"proteins":[166],"bromodomain":[169],"family":[170],"illustrate":[171],"extent":[173],"thermodynamics,":[180],"with":[181],"favorability":[183],"pharmacophore":[191],"probes":[192],"highly":[193],"dependent":[194],"composition":[197],"network":[201],"pocket":[204],"environment.":[205],"Given":[206],"ubiquity":[208],"networks":[211],"biologically":[213],"relevant":[214],"targets,":[216],"believe":[218],"our":[219],"approach":[220],"can":[221],"be":[222],"helpful":[223],"computer-aided":[225],"providing":[229],"pocket-specific":[231],"<i>a":[233],"priori</i>":[234],"systematic":[235],"consideration":[236],"selectivity.":[244]},"counts_by_year":[{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":4}],"updated_date":"2026-03-27T05:58:40.876381","created_date":"2025-10-10T00:00:00"}
