{"id":"https://openalex.org/W2011395228","doi":"https://doi.org/10.1021/ci8004397","title":"Grand Canonical Free-Energy Calculations of Protein\u2212Ligand Binding","display_name":"Grand Canonical Free-Energy Calculations of Protein\u2212Ligand Binding","publication_year":2009,"publication_date":"2009-03-23","ids":{"openalex":"https://openalex.org/W2011395228","doi":"https://doi.org/10.1021/ci8004397","mag":"2011395228","pmid":"https://pubmed.ncbi.nlm.nih.gov/19309088"},"language":"en","primary_location":{"id":"doi:10.1021/ci8004397","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ci8004397","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/A5083278176","display_name":"Matthew Clark","orcid":"https://orcid.org/0000-0002-9348-3528"},"institutions":[{"id":"https://openalex.org/I4210137215","display_name":"Inovio Pharmaceuticals (United States)","ror":"https://ror.org/042s6y882","country_code":"US","type":"company","lineage":["https://openalex.org/I4210137215"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Matthew Clark","raw_affiliation_strings":["Locus Pharmaceuticals, Four Valley Square, 512 Township Line Road, Blue Bell, Pennsylvania 19422","Locus Pharmaceuticals, Four Valley Square, 512 Township Line Road, Blue Bell, Pennsylvania 19422, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Locus Pharmaceuticals, Four Valley Square, 512 Township Line Road, Blue Bell, Pennsylvania 19422","institution_ids":[]},{"raw_affiliation_string":"Locus Pharmaceuticals, Four Valley Square, 512 Township Line Road, Blue Bell, Pennsylvania 19422, USA","institution_ids":["https://openalex.org/I4210137215"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5043562477","display_name":"Sia Meshkat","orcid":null},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sia Meshkat","raw_affiliation_strings":["Locus Pharmaceuticals, Four Valley Square, 512 Township Line Road, Blue Bell, Pennsylvania 19422"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Locus Pharmaceuticals, Four Valley Square, 512 Township Line Road, Blue Bell, Pennsylvania 19422","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5033139926","display_name":"Jeffrey S. Wiseman","orcid":"https://orcid.org/0000-0002-9304-4015"},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jeffrey S. Wiseman","raw_affiliation_strings":["Locus Pharmaceuticals, Four Valley Square, 512 Township Line Road, Blue Bell, Pennsylvania 19422"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Locus Pharmaceuticals, Four Valley Square, 512 Township Line Road, Blue Bell, Pennsylvania 19422","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5083278176"],"corresponding_institution_ids":["https://openalex.org/I4210137215"],"apc_list":null,"apc_paid":null,"fwci":1.8902,"has_fulltext":false,"cited_by_count":26,"citation_normalized_percentile":{"value":0.84878747,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"49","issue":"4","first_page":"934","last_page":"943"},"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":0.9994999766349792,"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/T10211","display_name":"Computational Drug Discovery Methods","score":0.9990000128746033,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/free-energy-perturbation","display_name":"Free energy perturbation","score":0.6539818048477173},{"id":"https://openalex.org/keywords/solvation","display_name":"Solvation","score":0.6381803750991821},{"id":"https://openalex.org/keywords/monte-carlo-method","display_name":"Monte Carlo method","score":0.5936442613601685},{"id":"https://openalex.org/keywords/computation","display_name":"Computation","score":0.5871991515159607},{"id":"https://openalex.org/keywords/statistical-physics","display_name":"Statistical physics","score":0.5865572690963745},{"id":"https://openalex.org/keywords/grand-canonical-ensemble","display_name":"Grand canonical ensemble","score":0.5818609595298767},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.4729960858821869},{"id":"https://openalex.org/keywords/thermodynamic-integration","display_name":"Thermodynamic integration","score":0.46531155705451965},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.44062933325767517},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.42273175716400146},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.32344335317611694},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.2914269268512726},{"id":"https://openalex.org/keywords/mathematics","display_name":"Mathematics","score":0.21427157521247864},{"id":"https://openalex.org/keywords/algorithm","display_name":"Algorithm","score":0.21176844835281372},{"id":"https://openalex.org/keywords/ion","display_name":"Ion","score":0.12332814931869507},{"id":"https://openalex.org/keywords/statistics","display_name":"Statistics","score":0.1001330316066742}],"concepts":[{"id":"https://openalex.org/C162641036","wikidata":"https://www.wikidata.org/wiki/Q5500215","display_name":"Free energy perturbation","level":3,"score":0.6539818048477173},{"id":"https://openalex.org/C148093993","wikidata":"https://www.wikidata.org/wiki/Q739398","display_name":"Solvation","level":3,"score":0.6381803750991821},{"id":"https://openalex.org/C19499675","wikidata":"https://www.wikidata.org/wiki/Q232207","display_name":"Monte Carlo method","level":2,"score":0.5936442613601685},{"id":"https://openalex.org/C45374587","wikidata":"https://www.wikidata.org/wiki/Q12525525","display_name":"Computation","level":2,"score":0.5871991515159607},{"id":"https://openalex.org/C121864883","wikidata":"https://www.wikidata.org/wiki/Q677916","display_name":"Statistical physics","level":1,"score":0.5865572690963745},{"id":"https://openalex.org/C29235156","wikidata":"https://www.wikidata.org/wiki/Q1153553","display_name":"Grand canonical ensemble","level":3,"score":0.5818609595298767},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.4729960858821869},{"id":"https://openalex.org/C141780669","wikidata":"https://www.wikidata.org/wiki/Q7783161","display_name":"Thermodynamic integration","level":3,"score":0.46531155705451965},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.44062933325767517},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.42273175716400146},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.32344335317611694},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.2914269268512726},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.21427157521247864},{"id":"https://openalex.org/C11413529","wikidata":"https://www.wikidata.org/wiki/Q8366","display_name":"Algorithm","level":1,"score":0.21176844835281372},{"id":"https://openalex.org/C145148216","wikidata":"https://www.wikidata.org/wiki/Q36496","display_name":"Ion","level":2,"score":0.12332814931869507},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.1001330316066742},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","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":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004735","descriptor_name":"Energy Transfer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004735","descriptor_name":"Energy Transfer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004735","descriptor_name":"Energy Transfer","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":"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":"D009113","descriptor_name":"Muramidase","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D009113","descriptor_name":"Muramidase","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D009113","descriptor_name":"Muramidase","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D009113","descriptor_name":"Muramidase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D009113","descriptor_name":"Muramidase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D009113","descriptor_name":"Muramidase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D015233","descriptor_name":"Models, Statistical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015233","descriptor_name":"Models, Statistical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015233","descriptor_name":"Models, Statistical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017122","descriptor_name":"Bacteriophage T4","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D017122","descriptor_name":"Bacteriophage T4","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D017122","descriptor_name":"Bacteriophage T4","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/ci8004397","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ci8004397","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:19309088","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/19309088","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":[{"id":"https://metadata.un.org/sdg/7","score":0.7599999904632568,"display_name":"Affordable and clean energy"}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":46,"referenced_works":["https://openalex.org/W408236731","https://openalex.org/W1555626538","https://openalex.org/W1573009101","https://openalex.org/W1597170374","https://openalex.org/W1625910593","https://openalex.org/W1970806934","https://openalex.org/W1981413816","https://openalex.org/W1994114759","https://openalex.org/W2001104449","https://openalex.org/W2001146548","https://openalex.org/W2004676220","https://openalex.org/W2005392415","https://openalex.org/W2007143784","https://openalex.org/W2009085431","https://openalex.org/W2017829285","https://openalex.org/W2030495049","https://openalex.org/W2033116315","https://openalex.org/W2037652551","https://openalex.org/W2043260710","https://openalex.org/W2046884185","https://openalex.org/W2049325087","https://openalex.org/W2053858804","https://openalex.org/W2056685038","https://openalex.org/W2064747164","https://openalex.org/W2065088630","https://openalex.org/W2077096083","https://openalex.org/W2080560949","https://openalex.org/W2083385781","https://openalex.org/W2086070714","https://openalex.org/W2089442765","https://openalex.org/W2092443343","https://openalex.org/W2095595785","https://openalex.org/W2107714804","https://openalex.org/W2114819818","https://openalex.org/W2117620409","https://openalex.org/W2118060715","https://openalex.org/W2121895929","https://openalex.org/W2122199548","https://openalex.org/W2122425162","https://openalex.org/W2131124255","https://openalex.org/W2143422060","https://openalex.org/W2154425964","https://openalex.org/W2160521062","https://openalex.org/W2161140363","https://openalex.org/W2463330796","https://openalex.org/W2949504121"],"related_works":["https://openalex.org/W2049601662","https://openalex.org/W2122685069","https://openalex.org/W2237020303","https://openalex.org/W2050023963","https://openalex.org/W4237654532","https://openalex.org/W2089807142","https://openalex.org/W3013936760","https://openalex.org/W3175840220","https://openalex.org/W2116929165","https://openalex.org/W2011395228"],"abstract_inverted_index":{"The":[0,31,60,93,148],"principles":[1],"behind":[2],"the":[3,15,27,75,127,140,143,162,171,181,198,205,211,227],"computation":[4,32],"of":[5,26,129,142,164,189,210,226],"protein-ligand":[6],"binding":[7,40,99,145,212,219],"free":[8,100,201,220],"energies":[9,101,108,221],"by":[10,36,109],"Monte":[11],"Carlo":[12],"simulation":[13,96,151,172,199],"in":[14,21,139],"Grand":[16,94,149],"Canonical":[17,95,150],"Ensemble":[18],"are":[19,29,80,222],"described":[20],"detail,":[22],"and":[23,78,175,229],"two":[24],"variations":[25],"calculation":[28],"presented.":[30],"can":[33,103,176],"be":[34,104,168,177],"performed":[35],"bathing":[37],"a":[38,135,223],"protein":[39],"site":[41],"either":[42],"with":[43,48,52,90,121,185],"ligand":[44,53,86],"images":[45,54,87],"that":[46,55,70,88,102,119,161,166,218],"interact":[47,89],"each":[49,58,91],"other":[50],"or":[51,208],"pass":[56],"through":[57],"other.":[59,92],"second":[61],"method":[62],"is":[63,134,160,173,200,217,232],"theoretically":[64],"more":[65,183],"rigorous,":[66],"but":[67],"we":[68],"show":[69],"both":[71],"methods":[72],"lead":[73],"to":[74,84,106,116,156,187,194,234],"same":[76],"result,":[77],"there":[79],"distinct":[81],"numeric":[82],"advantages":[83],"using":[85],"provides":[97],"gas-phase":[98],"converted":[105],"aqueous":[107],"generalized":[110],"Born-surface":[111],"area":[112],"(GB/SA)":[113],"solvation":[114,132],"calculations":[115,133],"provide":[117],"values":[118],"agree":[120],"experiment":[122],"within":[123],"+/-1.5":[124],"kcal/mol.":[125],"However,":[126],"accuracy":[128,141],"these":[130],"simple":[131],"major":[136],"limiting":[137],"factor":[138],"overall":[144],"free-energy":[146,157],"computation.":[147],"has":[152],"several":[153],"characteristics":[154],"beneficial":[155],"calculations.":[158],"One":[159],"number":[163],"parameters":[165],"must":[167],"set":[169],"for":[170],"small":[174],"determined":[178],"objectively,":[179],"making":[180],"outcome":[182,225],"deterministic,":[184],"respect":[186],"choice":[188],"input":[190],"conditions,":[191],"as":[192],"compared":[193],"perturbation":[195],"methods.":[196],"Second,":[197],"from":[202],"assumptions":[203],"about":[204],"starting":[206],"pose":[207],"nature":[209],"site.":[213],"A":[214],"final":[215],"benefit":[216],"direct":[224],"simulation,":[228],"little":[230],"processing":[231],"required":[233],"determine":[235],"them.":[236]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2021,"cited_by_count":1},{"year":2020,"cited_by_count":2},{"year":2019,"cited_by_count":1},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":1},{"year":2015,"cited_by_count":3},{"year":2014,"cited_by_count":2},{"year":2012,"cited_by_count":6}],"updated_date":"2026-06-15T08:34:33.830935","created_date":"2025-10-10T00:00:00"}
