{"id":"https://openalex.org/W2261529249","doi":"https://doi.org/10.1021/acs.jcim.5b00259","title":"Toward Focusing Conformational Ensembles on Bioactive Conformations: A Molecular Mechanics/Quantum Mechanics Study","display_name":"Toward Focusing Conformational Ensembles on Bioactive Conformations: A Molecular Mechanics/Quantum Mechanics Study","publication_year":2015,"publication_date":"2015-09-25","ids":{"openalex":"https://openalex.org/W2261529249","doi":"https://doi.org/10.1021/acs.jcim.5b00259","mag":"2261529249","pmid":"https://pubmed.ncbi.nlm.nih.gov/26406154"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5b00259","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5b00259","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/A5027015261","display_name":"Hannah H. Avgy-David","orcid":null},"institutions":[{"id":"https://openalex.org/I13955877","display_name":"Bar-Ilan University","ror":"https://ror.org/03kgsv495","country_code":"IL","type":"education","lineage":["https://openalex.org/I13955877"]}],"countries":["IL"],"is_corresponding":true,"raw_author_name":"Hannah H. Avgy-David","raw_affiliation_strings":["Department of Chemistry, Bar Ilan University, Ramat-Gan 52900, Israel"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Bar Ilan University, Ramat-Gan 52900, Israel","institution_ids":["https://openalex.org/I13955877"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5010899423","display_name":"Hanoch Senderowitz","orcid":"https://orcid.org/0000-0003-0076-1355"},"institutions":[{"id":"https://openalex.org/I13955877","display_name":"Bar-Ilan University","ror":"https://ror.org/03kgsv495","country_code":"IL","type":"education","lineage":["https://openalex.org/I13955877"]}],"countries":["IL"],"is_corresponding":false,"raw_author_name":"Hanoch Senderowitz","raw_affiliation_strings":["Department of Chemistry, Bar Ilan University, Ramat-Gan 52900, Israel"],"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Bar Ilan University, Ramat-Gan 52900, Israel","institution_ids":["https://openalex.org/I13955877"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5027015261"],"corresponding_institution_ids":["https://openalex.org/I13955877"],"apc_list":null,"apc_paid":null,"fwci":4.3596,"has_fulltext":false,"cited_by_count":32,"citation_normalized_percentile":{"value":0.9490324,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":90,"max":99},"biblio":{"volume":"55","issue":"10","first_page":"2154","last_page":"2167"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9998999834060669,"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":0.9998999834060669,"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":0.9979000091552734,"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":0.9957000017166138,"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/maxima-and-minima","display_name":"Maxima and minima","score":0.7596148252487183},{"id":"https://openalex.org/keywords/conformational-ensembles","display_name":"Conformational ensembles","score":0.6992106437683105},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.615324854850769},{"id":"https://openalex.org/keywords/protein-data-bank","display_name":"Protein Data Bank (RCSB PDB)","score":0.5270048975944519},{"id":"https://openalex.org/keywords/molecular-mechanics","display_name":"Molecular mechanics","score":0.5093913674354553},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.5079939961433411},{"id":"https://openalex.org/keywords/force-field","display_name":"Force field (fiction)","score":0.4995875358581543},{"id":"https://openalex.org/keywords/energy-landscape","display_name":"Energy landscape","score":0.4943573474884033},{"id":"https://openalex.org/keywords/bound-state","display_name":"Bound state","score":0.4483201205730438},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.44417813420295715},{"id":"https://openalex.org/keywords/work","display_name":"Work (physics)","score":0.44371458888053894},{"id":"https://openalex.org/keywords/chemical-physics","display_name":"Chemical physics","score":0.3522609770298004},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.2886597514152527},{"id":"https://openalex.org/keywords/stereochemistry","display_name":"Stereochemistry","score":0.2602739930152893},{"id":"https://openalex.org/keywords/thermodynamics","display_name":"Thermodynamics","score":0.24516990780830383},{"id":"https://openalex.org/keywords/quantum-mechanics","display_name":"Quantum mechanics","score":0.15479165315628052},{"id":"https://openalex.org/keywords/mathematics","display_name":"Mathematics","score":0.10827401280403137}],"concepts":[{"id":"https://openalex.org/C186633575","wikidata":"https://www.wikidata.org/wiki/Q845060","display_name":"Maxima and minima","level":2,"score":0.7596148252487183},{"id":"https://openalex.org/C2777936996","wikidata":"https://www.wikidata.org/wiki/Q17148461","display_name":"Conformational ensembles","level":3,"score":0.6992106437683105},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.615324854850769},{"id":"https://openalex.org/C65556437","wikidata":"https://www.wikidata.org/wiki/Q766195","display_name":"Protein Data Bank (RCSB PDB)","level":2,"score":0.5270048975944519},{"id":"https://openalex.org/C25057246","wikidata":"https://www.wikidata.org/wiki/Q1344441","display_name":"Molecular mechanics","level":3,"score":0.5093913674354553},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.5079939961433411},{"id":"https://openalex.org/C10803110","wikidata":"https://www.wikidata.org/wiki/Q1341441","display_name":"Force field (fiction)","level":2,"score":0.4995875358581543},{"id":"https://openalex.org/C119621388","wikidata":"https://www.wikidata.org/wiki/Q5377166","display_name":"Energy landscape","level":2,"score":0.4943573474884033},{"id":"https://openalex.org/C174084160","wikidata":"https://www.wikidata.org/wiki/Q908049","display_name":"Bound state","level":2,"score":0.4483201205730438},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.44417813420295715},{"id":"https://openalex.org/C18762648","wikidata":"https://www.wikidata.org/wiki/Q42213","display_name":"Work (physics)","level":2,"score":0.44371458888053894},{"id":"https://openalex.org/C159467904","wikidata":"https://www.wikidata.org/wiki/Q2001702","display_name":"Chemical physics","level":1,"score":0.3522609770298004},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.2886597514152527},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.2602739930152893},{"id":"https://openalex.org/C97355855","wikidata":"https://www.wikidata.org/wiki/Q11473","display_name":"Thermodynamics","level":1,"score":0.24516990780830383},{"id":"https://openalex.org/C62520636","wikidata":"https://www.wikidata.org/wiki/Q944","display_name":"Quantum mechanics","level":1,"score":0.15479165315628052},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.10827401280403137},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0},{"id":"https://openalex.org/C134306372","wikidata":"https://www.wikidata.org/wiki/Q7754","display_name":"Mathematical analysis","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016503","descriptor_name":"Drug Delivery Systems","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016503","descriptor_name":"Drug Delivery Systems","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016503","descriptor_name":"Drug Delivery Systems","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":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","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":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.5b00259","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5b00259","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:26406154","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/26406154","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","display_name":"Affordable and clean energy","score":0.8500000238418579}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":38,"referenced_works":["https://openalex.org/W78747592","https://openalex.org/W1480654101","https://openalex.org/W1892938473","https://openalex.org/W1974625550","https://openalex.org/W1978705163","https://openalex.org/W1980019773","https://openalex.org/W1990627326","https://openalex.org/W1998264260","https://openalex.org/W2002987877","https://openalex.org/W2022659284","https://openalex.org/W2025624195","https://openalex.org/W2025880494","https://openalex.org/W2044038786","https://openalex.org/W2047730466","https://openalex.org/W2051381895","https://openalex.org/W2051419785","https://openalex.org/W2053050028","https://openalex.org/W2053333781","https://openalex.org/W2058433776","https://openalex.org/W2063906445","https://openalex.org/W2064747164","https://openalex.org/W2066962978","https://openalex.org/W2068351024","https://openalex.org/W2069344005","https://openalex.org/W2077467665","https://openalex.org/W2078082523","https://openalex.org/W2087376769","https://openalex.org/W2092157292","https://openalex.org/W2094839792","https://openalex.org/W2096196180","https://openalex.org/W2096929343","https://openalex.org/W2098515641","https://openalex.org/W2109415161","https://openalex.org/W2124026197","https://openalex.org/W2127073449","https://openalex.org/W2131366727","https://openalex.org/W2147421370","https://openalex.org/W2162166182"],"related_works":["https://openalex.org/W2007369531","https://openalex.org/W1996733108","https://openalex.org/W1988279278","https://openalex.org/W2182607276","https://openalex.org/W2081461182","https://openalex.org/W4294771207","https://openalex.org/W2036866634","https://openalex.org/W2129071110","https://openalex.org/W4253114884","https://openalex.org/W2019723230"],"abstract_inverted_index":{"The":[0,200],"identification":[1],"of":[2,61,66,74,112,134,143,169,242,313,325,334],"bound":[3,67,150,210,250,298,328,347],"conformations,":[4],"namely,":[5],"conformations":[6,23,44,70,111,153],"adopted":[7],"by":[8,33,117,122,176,213],"ligands":[9,114],"when":[10,302],"binding":[11],"their":[12,118],"target":[13],"is":[14],"critical":[15],"for":[16,71,293],"target-based":[17],"and":[18,63,68,99,106,147,167,181,192,232,311,318,322,348],"ligand-based":[19],"drug":[20],"design.":[21],"Bound":[22,110],"could":[24,290],"be":[25,222,291],"obtained":[26,90,164,252],"computationally":[27],"from":[28],"unbound":[29,69,136,145,244,349],"conformational":[30,34,86,295],"ensembles":[31,87,174,296],"generated":[32,175],"search":[35],"tools.":[36],"However,":[37],"these":[38,125],"tools":[39],"also":[40],"generate":[41],"many":[42],"nonrelevant":[43],"thus":[45],"requiring":[46],"a":[47,53,59,72,238,254,263],"focusing":[48,294],"mechanism.":[49],"To":[50],"identify":[51],"such":[52],"mechanism,":[54],"this":[55,340],"work":[56,341],"focuses":[57],"on":[58,297],"comparison":[60],"energies":[62,142],"structural":[64,336],"properties":[65],"set":[73],"FDA":[75],"approved":[76],"drugs":[77],"whose":[78],"complexes":[79],"are":[80],"available":[81],"in":[82,165,188,339],"the":[83,102,135,139,144,148,156,170,173,177,182,205,209,229,243,249,258,314,327,335],"PDB.":[84],"Unbound":[85],"were":[88,96,115,129,163],"initially":[89],"with":[91,226,235,253,262],"three":[92],"force":[93,104,179,284],"fields.":[94],"These":[95,287],"merged,":[97],"clustered,":[98],"reminimized":[100,183],"using":[101,172,257,303],"same":[103],"fields":[105,180],"four":[107],"QM":[108,277,316],"methods.":[109,286],"all":[113],"represented":[116],"crystal":[119],"structures":[120],"or":[121,138,261],"approximations":[123,247],"to":[124,221,228,237,248,308,344],"structures.":[126],"Energy":[127],"differences":[128,282],"calculated":[130],"between":[131,346],"global":[132,197,230],"minima":[133],"state":[137],"Boltzmann":[140,239],"averaged":[141,240],"ensemble":[146],"approximated":[149],"conformations.":[151,299,350],"Ligand":[152],"which":[154,204,306],"resemble":[155],"X-ray":[157],"conformation":[158,211,251],"(RMSD":[159],"<":[160],"1.0":[161],"\u00c5)":[162],"91%-97%":[166],"96%-98%":[168],"cases":[171],"individual":[178],"ensembles,":[184,315],"respectively,":[185],"yet":[186],"only":[187],"52%-56%":[189],"(original":[190],"ensembles)":[191,195],"47%-65%":[193],"(reminimized":[194],"as":[196],"energy":[198,201,217,241,281,288,304],"minima.":[199],"window":[202],"within":[203],"different":[206],"methods":[207,278,317],"identified":[208],"(approximated":[212],"its":[214],"closest":[215],"local":[216],"minimum)":[218],"was":[219,342],"found":[220],"at":[223],"4-6":[224],"kcal/mol":[225],"respect":[227,236],"minimum":[231],"marginally":[233],"lower":[234,272,280],"ensemble.":[245],"Better":[246],"constrained":[255],"minimization":[256],"crystallographic":[259],"B-factors":[260],"newly":[264],"developed":[265],"Knee":[266],"Point":[267],"Detection":[268],"(KPD)":[269],"method":[270],"gave":[271,279],"values":[273],"(2-5":[274],"kcal/mol).":[275],"Overall,":[276],"than":[283],"field":[285],"thresholds":[289],"used":[292],"For":[300],"example,":[301],"cutoffs":[305],"corresponded":[307],"retaining":[309],"50%":[310],"70%":[312],"CHARMm":[319],"offer":[320],"60-65%":[321],"80-84%":[323],"probability":[324],"obtaining":[326],"conformation,":[329],"respectively.":[330],"In":[331],"contrast,":[332],"none":[333],"criteria":[337],"considered":[338],"able":[343],"differentiate":[345]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":4},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":7},{"year":2019,"cited_by_count":3},{"year":2018,"cited_by_count":2},{"year":2017,"cited_by_count":6},{"year":2016,"cited_by_count":2},{"year":2015,"cited_by_count":2}],"updated_date":"2026-04-04T16:13:02.066488","created_date":"2025-10-10T00:00:00"}
