{"id":"https://openalex.org/W4410997423","doi":"https://doi.org/10.1021/acs.jcim.5c00704","title":"Simple Method to Optimize the Spacing and Number of Alchemical Intermediates in Expanded Ensemble Free Energy Calculations","display_name":"Simple Method to Optimize the Spacing and Number of Alchemical Intermediates in Expanded Ensemble Free Energy Calculations","publication_year":2025,"publication_date":"2025-06-03","ids":{"openalex":"https://openalex.org/W4410997423","doi":"https://doi.org/10.1021/acs.jcim.5c00704","pmid":"https://pubmed.ncbi.nlm.nih.gov/40459175"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c00704","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00704","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/A5003341058","display_name":"Dylan Novack","orcid":"https://orcid.org/0000-0003-1434-0316"},"institutions":[{"id":"https://openalex.org/I2801004183","display_name":"Temple College","ror":"https://ror.org/038s1ax16","country_code":"US","type":"education","lineage":["https://openalex.org/I2801004183"]},{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dylan Novack","raw_affiliation_strings":["Department of Chemistry","Temple University"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry","institution_ids":[]},{"raw_affiliation_string":"Temple University","institution_ids":["https://openalex.org/I2801004183","https://openalex.org/I84392919"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5028185893","display_name":"Robert M. Raddi","orcid":"https://orcid.org/0000-0001-7139-5028"},"institutions":[{"id":"https://openalex.org/I2801004183","display_name":"Temple College","ror":"https://ror.org/038s1ax16","country_code":"US","type":"education","lineage":["https://openalex.org/I2801004183"]},{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Robert M. Raddi","raw_affiliation_strings":["Department of Chemistry","Temple University"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry","institution_ids":[]},{"raw_affiliation_string":"Temple University","institution_ids":["https://openalex.org/I2801004183","https://openalex.org/I84392919"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100763903","display_name":"Si Zhang","orcid":"https://orcid.org/0000-0002-1164-2020"},"institutions":[{"id":"https://openalex.org/I2801004183","display_name":"Temple College","ror":"https://ror.org/038s1ax16","country_code":"US","type":"education","lineage":["https://openalex.org/I2801004183"]},{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Si Zhang","raw_affiliation_strings":["Department of Chemistry","Temple University"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry","institution_ids":[]},{"raw_affiliation_string":"Temple University","institution_ids":["https://openalex.org/I2801004183","https://openalex.org/I84392919"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5030167744","display_name":"Matthew F. D. Hurley","orcid":null},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]},{"id":"https://openalex.org/I2801004183","display_name":"Temple College","ror":"https://ror.org/038s1ax16","country_code":"US","type":"education","lineage":["https://openalex.org/I2801004183"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Matthew F. D. Hurley","raw_affiliation_strings":["Department of Chemistry","Temple University"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry","institution_ids":[]},{"raw_affiliation_string":"Temple University","institution_ids":["https://openalex.org/I2801004183","https://openalex.org/I84392919"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5074806960","display_name":"Vincent A. Voelz","orcid":"https://orcid.org/0000-0002-1054-2124"},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]},{"id":"https://openalex.org/I2801004183","display_name":"Temple College","ror":"https://ror.org/038s1ax16","country_code":"US","type":"education","lineage":["https://openalex.org/I2801004183"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Vincent A. Voelz","raw_affiliation_strings":["Department of Chemistry","Temple University"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry","institution_ids":[]},{"raw_affiliation_string":"Temple University","institution_ids":["https://openalex.org/I2801004183","https://openalex.org/I84392919"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5074806960"],"corresponding_institution_ids":["https://openalex.org/I2801004183","https://openalex.org/I84392919"],"apc_list":null,"apc_paid":null,"fwci":4.9548,"has_fulltext":false,"cited_by_count":3,"citation_normalized_percentile":{"value":0.95200023,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":95,"max":99},"biblio":{"volume":"65","issue":"12","first_page":"6089","last_page":"6101"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"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"}},"topics":[{"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"}},{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.998199999332428,"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":0.9955999851226807,"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/simple","display_name":"Simple (philosophy)","score":0.8571393489837646},{"id":"https://openalex.org/keywords/energy","display_name":"Energy (signal processing)","score":0.6057917475700378},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.5014870166778564},{"id":"https://openalex.org/keywords/alchemy","display_name":"Alchemy","score":0.4882991313934326},{"id":"https://openalex.org/keywords/statistical-physics","display_name":"Statistical physics","score":0.43866002559661865},{"id":"https://openalex.org/keywords/algorithm","display_name":"Algorithm","score":0.3796635866165161},{"id":"https://openalex.org/keywords/mathematics","display_name":"Mathematics","score":0.29298195242881775},{"id":"https://openalex.org/keywords/statistics","display_name":"Statistics","score":0.21915173530578613},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.2126045525074005},{"id":"https://openalex.org/keywords/art-history","display_name":"Art history","score":0.05977827310562134}],"concepts":[{"id":"https://openalex.org/C2780586882","wikidata":"https://www.wikidata.org/wiki/Q7520643","display_name":"Simple (philosophy)","level":2,"score":0.8571393489837646},{"id":"https://openalex.org/C186370098","wikidata":"https://www.wikidata.org/wiki/Q442787","display_name":"Energy (signal processing)","level":2,"score":0.6057917475700378},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.5014870166778564},{"id":"https://openalex.org/C174468945","wikidata":"https://www.wikidata.org/wiki/Q39689","display_name":"Alchemy","level":2,"score":0.4882991313934326},{"id":"https://openalex.org/C121864883","wikidata":"https://www.wikidata.org/wiki/Q677916","display_name":"Statistical physics","level":1,"score":0.43866002559661865},{"id":"https://openalex.org/C11413529","wikidata":"https://www.wikidata.org/wiki/Q8366","display_name":"Algorithm","level":1,"score":0.3796635866165161},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.29298195242881775},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.21915173530578613},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.2126045525074005},{"id":"https://openalex.org/C52119013","wikidata":"https://www.wikidata.org/wiki/Q50637","display_name":"Art history","level":1,"score":0.05977827310562134},{"id":"https://openalex.org/C138885662","wikidata":"https://www.wikidata.org/wiki/Q5891","display_name":"Philosophy","level":0,"score":0.0},{"id":"https://openalex.org/C111472728","wikidata":"https://www.wikidata.org/wiki/Q9471","display_name":"Epistemology","level":1,"score":0.0},{"id":"https://openalex.org/C142362112","wikidata":"https://www.wikidata.org/wiki/Q735","display_name":"Art","level":0,"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":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","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":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.5c00704","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00704","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:40459175","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/40459175","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":0.8700000047683716,"id":"https://metadata.un.org/sdg/7"}],"awards":[{"id":"https://openalex.org/G1017287825","display_name":null,"funder_award_id":"W911NF-16-2-0189","funder_id":"https://openalex.org/F4320338295","funder_display_name":"Army Research Laboratory"},{"id":"https://openalex.org/G4135459561","display_name":null,"funder_award_id":"1625061","funder_id":"https://openalex.org/F4320337388","funder_display_name":"Division of Computer and Network Systems"},{"id":"https://openalex.org/G8698437761","display_name":null,"funder_award_id":"R01GM123296","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"}],"funders":[{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"},{"id":"https://openalex.org/F4320337388","display_name":"Division of Computer and Network Systems","ror":"https://ror.org/02rdzmk74"},{"id":"https://openalex.org/F4320338295","display_name":"Army Research Laboratory","ror":"https://ror.org/011hc8f90"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":62,"referenced_works":["https://openalex.org/W1031578623","https://openalex.org/W1976499671","https://openalex.org/W1977151908","https://openalex.org/W1977234725","https://openalex.org/W1982306719","https://openalex.org/W2003582562","https://openalex.org/W2018736104","https://openalex.org/W2024762727","https://openalex.org/W2039771689","https://openalex.org/W2040809566","https://openalex.org/W2047676282","https://openalex.org/W2050617474","https://openalex.org/W2057806291","https://openalex.org/W2059206957","https://openalex.org/W2063206968","https://openalex.org/W2070913259","https://openalex.org/W2084523245","https://openalex.org/W2085213650","https://openalex.org/W2089435371","https://openalex.org/W2098044543","https://openalex.org/W2114227821","https://openalex.org/W2154670681","https://openalex.org/W2155554859","https://openalex.org/W2275226577","https://openalex.org/W2404280981","https://openalex.org/W2554947919","https://openalex.org/W2582687887","https://openalex.org/W2587480998","https://openalex.org/W2759860792","https://openalex.org/W2772606519","https://openalex.org/W2952105231","https://openalex.org/W2969038621","https://openalex.org/W2979711643","https://openalex.org/W2990010612","https://openalex.org/W3047663514","https://openalex.org/W3083406432","https://openalex.org/W3087004338","https://openalex.org/W3102529165","https://openalex.org/W3105581675","https://openalex.org/W3111206976","https://openalex.org/W3163051848","https://openalex.org/W3164542691","https://openalex.org/W3164625824","https://openalex.org/W4212835619","https://openalex.org/W4243546559","https://openalex.org/W4321083912","https://openalex.org/W4322603972","https://openalex.org/W4376226284","https://openalex.org/W4378212112","https://openalex.org/W4385874260","https://openalex.org/W4386305294","https://openalex.org/W4387334097","https://openalex.org/W4388877334","https://openalex.org/W4390049362","https://openalex.org/W4390339927","https://openalex.org/W4391972455","https://openalex.org/W4397293207","https://openalex.org/W4402406955","https://openalex.org/W4402711692","https://openalex.org/W4405981631","https://openalex.org/W4406199147","https://openalex.org/W6947848574"],"related_works":["https://openalex.org/W2327690717","https://openalex.org/W1570968926","https://openalex.org/W2033179625","https://openalex.org/W4253737202","https://openalex.org/W2367275899","https://openalex.org/W599555033","https://openalex.org/W2502020699","https://openalex.org/W2500372171","https://openalex.org/W2608373345","https://openalex.org/W2026546269"],"abstract_inverted_index":{"Alchemical":[0],"free":[1,30,47,82,98,184,198],"energy":[2,31,48,83,99,185,199],"calculations":[3,12],"are":[4,13],"essential":[5],"to":[6,27,77,105,196],"modern":[7],"structure-based":[8],"drug":[9],"design.":[10],"Such":[11],"usually":[14],"performed":[15],"at":[16],"a":[17,23,75,130,139,166,176,206,227],"series":[18],"of":[19,37,45,55,65,94,110,134,145,215],"discrete":[20],"intermediates":[21,96,147],"along":[22],"nonphysical":[24],"thermodynamic":[25,66,107],"pathway":[26],"estimate":[28,49],"the":[29,46,53,63,92,106,143,154,162,212],"difference":[32],"between":[33],"two":[34],"end":[35],"points":[36],"an":[38,88,149,180],"alchemical":[39,56,79,95,146,181],"transformation.":[40],"The":[41],"efficiency":[42],"and":[43,68,137,170],"accuracy":[44],"depends":[50],"critically":[51],"on":[52,153],"choice":[54,93],"intermediates.":[57],"In":[58],"this":[59],"paper,":[60],"we":[61],"review":[62],"concept":[64],"length,":[67],"how":[69,161,190],"it":[70],"can":[71,193],"be":[72,194],"used":[73,195],"as":[74],"principle":[76],"choose":[78],"paths":[80],"in":[81,97,148,165,175,201,211,226],"simulations.":[84,100,125],"We":[85,158,187,220],"then":[86,171],"present":[87],"algorithm":[89,109,225],"for":[90,119,141,179,208],"optimizing":[91,142],"Our":[101,126],"method":[102,127,140,163,192],"is":[103],"similar":[104],"trailblazing":[108],"Rizzi":[111],"et":[112],"al.":[113],"(2020),":[114],"but":[115],"with":[116,121],"several":[117],"improvements":[118],"use":[120,174],"expanded":[122],"ensemble":[123],"(EE)":[124],"only":[128],"requires":[129],"single":[131],"initial":[132],"round":[133],"EE":[135,150],"simulation":[136,151],"includes":[138],"number":[144],"based":[152],"predicted":[155],"mixing":[156],"time.":[157],"first":[159],"show":[160,189],"performs":[164],"simple":[167],"toy":[168],"model,":[169],"demonstrate":[172],"its":[173],"realistic":[177],"example":[178],"relative":[182],"thermostability":[183],"calculation.":[186],"also":[188],"our":[191,223],"optimize":[197],"estimates":[200],"other":[202],"contexts,":[203],"namely,":[204],"calculating":[205],"score":[207],"model":[209],"selection":[210],"Bayesian":[213],"Inference":[214],"Conformational":[216],"Populations":[217],"(BICePs)":[218],"approach.":[219],"have":[221],"implemented":[222],"optimization":[224],"freely":[228],"available":[229],"Python":[230],"package":[231],"called":[232],"<i>pylambdaopt</i>":[233],"(https://github.com/vvoelz/pylambdaopt).":[234]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":2}],"updated_date":"2025-11-06T03:46:38.306776","created_date":"2025-10-10T00:00:00"}
