{"id":"https://openalex.org/W2089675463","doi":"https://doi.org/10.1002/prot.20105","title":"Molecular determinants of thapsigargin binding by SERCA Ca2+\u2010ATPase: A computational docking study","display_name":"Molecular determinants of thapsigargin binding by SERCA Ca2+\u2010ATPase: A computational docking study","publication_year":2004,"publication_date":"2004-05-20","ids":{"openalex":"https://openalex.org/W2089675463","doi":"https://doi.org/10.1002/prot.20105","mag":"2089675463","pmid":"https://pubmed.ncbi.nlm.nih.gov/15229891"},"language":"en","primary_location":{"id":"doi:10.1002/prot.20105","doi":"https://doi.org/10.1002/prot.20105","is_oa":false,"landing_page_url":"https://doi.org/10.1002/prot.20105","pdf_url":null,"source":{"id":"https://openalex.org/S121161810","display_name":"Proteins Structure Function and Bioinformatics","issn_l":"0887-3585","issn":["0887-3585","1097-0134"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proteins: Structure, Function, and Bioinformatics","raw_type":"journal-article"},"volume":null,"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/A5014690422","display_name":"Stefan Paula","orcid":"https://orcid.org/0000-0003-4100-1467","observed_orcids":["https://orcid.org/0000-0003-4100-1467"]},"institutions":[{"id":"https://openalex.org/I63135867","display_name":"University of Cincinnati","ror":"https://ror.org/01e3m7079","country_code":"US","type":"education","lineage":["https://openalex.org/I63135867"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Stefan Paula","raw_affiliation_strings":["Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267-0575, USA. paulas@email.uc.edu","Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267-0575, USA. paulas@email.uc.edu","institution_ids":["https://openalex.org/I63135867"]},{"raw_affiliation_string":"Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575, USA","institution_ids":["https://openalex.org/I63135867"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5111656293","display_name":"William James Ball","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I63135867","display_name":"University of Cincinnati","ror":"https://ror.org/01e3m7079","country_code":"US","type":"education","lineage":["https://openalex.org/I63135867"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"William James Ball","raw_affiliation_strings":["Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Cincinnati, Ohio"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Cincinnati, Ohio","institution_ids":["https://openalex.org/I63135867"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5014690422"],"corresponding_institution_ids":["https://openalex.org/I63135867"],"apc_list":{"value":4550,"currency":"USD","value_usd":4550},"apc_paid":null,"fwci":1.3906,"has_fulltext":false,"cited_by_count":30,"citation_normalized_percentile":{"value":0.81744102,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":97},"biblio":{"volume":"56","issue":"3","first_page":"595","last_page":"606"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.8208000063896179,"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":0.8208000063896179,"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":0.057100001722574234,"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/T11204","display_name":"Ion Channels and Receptors","score":0.028300000354647636,"subfield":{"id":"https://openalex.org/subfields/2809","display_name":"Sensory Systems"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/thapsigargin","display_name":"thapsigargin","score":1.0},{"id":"https://openalex.org/keywords/serca1a","display_name":"SERCA1a","score":0.9430000185966492},{"id":"https://openalex.org/keywords/sarco-endoplasmic-reticulum-ca2-atpase","display_name":"sarco/endoplasmic reticulum Ca2+-ATPase","score":0.9570000171661377},{"id":"https://openalex.org/keywords/ligand-binding","display_name":"ligand binding","score":0.777999997138977},{"id":"https://openalex.org/keywords/hydrophobic-interactions","display_name":"hydrophobic interactions","score":0.9110000133514404},{"id":"https://openalex.org/keywords/calcium-pump-inhibition","display_name":"calcium pump inhibition","score":0.460999995470047},{"id":"https://openalex.org/keywords/binding-affinity-prediction","display_name":"binding affinity prediction","score":0.652999997138977}],"concepts":[{"id":"https://openalex.org/C2781414619","wikidata":"https://www.wikidata.org/wiki/Q24785512","display_name":"SERCA","level":4,"score":0.8598910570144653},{"id":"https://openalex.org/C2777146706","wikidata":"https://www.wikidata.org/wiki/Q3981006","display_name":"Thapsigargin","level":3,"score":0.7903115153312683},{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.764918863773346},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7375483512878418},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.65242999792099},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.5307424068450928},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.4818631112575531},{"id":"https://openalex.org/C158617107","wikidata":"https://www.wikidata.org/wiki/Q79927","display_name":"Endoplasmic reticulum","level":2,"score":0.47210636734962463},{"id":"https://openalex.org/C23265538","wikidata":"https://www.wikidata.org/wiki/Q300033","display_name":"ATPase","level":3,"score":0.46432986855506897},{"id":"https://openalex.org/C178910836","wikidata":"https://www.wikidata.org/wiki/Q2196961","display_name":"Molecular model","level":2,"score":0.4470686912536621},{"id":"https://openalex.org/C2780283098","wikidata":"https://www.wikidata.org/wiki/Q4688960","display_name":"Affinities","level":2,"score":0.43779557943344116},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.37978848814964294},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.32839080691337585},{"id":"https://openalex.org/C8010536","wikidata":"https://www.wikidata.org/wiki/Q160398","display_name":"Crystallography","level":1,"score":0.32778242230415344},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2510506510734558},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.1161298155784607},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.0},{"id":"https://openalex.org/C159110408","wikidata":"https://www.wikidata.org/wiki/Q121176","display_name":"Nursing","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000252","descriptor_name":"Calcium-Transporting ATPases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D000252","descriptor_name":"Calcium-Transporting ATPases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"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":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008432","descriptor_name":"Mathematical Computing","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","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":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012984","descriptor_name":"Software","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":"D016297","descriptor_name":"Mutagenesis, Site-Directed","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019284","descriptor_name":"Thapsigargin","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D019284","descriptor_name":"Thapsigargin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019943","descriptor_name":"Amino Acid Substitution","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D053498","descriptor_name":"Sarcoplasmic Reticulum Calcium-Transporting ATPases","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D057927","descriptor_name":"Hydrophobic and Hydrophilic Interactions","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1002/prot.20105","doi":"https://doi.org/10.1002/prot.20105","is_oa":false,"landing_page_url":"https://doi.org/10.1002/prot.20105","pdf_url":null,"source":{"id":"https://openalex.org/S121161810","display_name":"Proteins Structure Function and Bioinformatics","issn_l":"0887-3585","issn":["0887-3585","1097-0134"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proteins: Structure, Function, and Bioinformatics","raw_type":"journal-article"},{"id":"pmid:15229891","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/15229891","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,"listed_in":[],"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":"Proteins","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":31,"referenced_works":["https://openalex.org/W19906052","https://openalex.org/W1488722525","https://openalex.org/W1501972593","https://openalex.org/W1530822737","https://openalex.org/W1605578858","https://openalex.org/W1897434666","https://openalex.org/W1973191530","https://openalex.org/W1977033920","https://openalex.org/W1980949045","https://openalex.org/W1983986975","https://openalex.org/W1992475843","https://openalex.org/W1995653946","https://openalex.org/W2017757270","https://openalex.org/W2045437907","https://openalex.org/W2047877365","https://openalex.org/W2050456292","https://openalex.org/W2059341988","https://openalex.org/W2077546705","https://openalex.org/W2087726424","https://openalex.org/W2091734240","https://openalex.org/W2093873733","https://openalex.org/W2098550162","https://openalex.org/W2103300124","https://openalex.org/W2112918122","https://openalex.org/W2114663994","https://openalex.org/W2116449821","https://openalex.org/W2118128739","https://openalex.org/W2128607364","https://openalex.org/W2131910418","https://openalex.org/W2153331570","https://openalex.org/W2405153371"],"related_works":["https://openalex.org/W2112115708","https://openalex.org/W2053118944","https://openalex.org/W2973973006","https://openalex.org/W1488722525","https://openalex.org/W2118128739","https://openalex.org/W2042068397","https://openalex.org/W2070348954","https://openalex.org/W1976127135","https://openalex.org/W1982216737","https://openalex.org/W1501972593"],"abstract_inverted_index":{"Thapsigargin":[0],"(TG)":[1],"is":[2],"a":[3,93,181,204,217,231,289],"potent":[4],"and":[5,34,53,84,102,172,280],"commonly":[6],"used":[7],"inhibitor":[8],"of":[9,14,26,51,81,87,112,196,200,211,225,240,251,272],"the":[10,21,31,45,56,59,70,78,82,99,108,122,126,132,142,155,169,193,197,201,221,226,235,241,273],"ion":[11],"transport":[12],"activity":[13],"sarco/endoplasmic":[15],"reticulum":[16],"Ca2+-ATPases":[17],"(SERCA).":[18],"Based":[19],"on":[20,154],"recently":[22],"published":[23],"crystal":[24,100],"structures":[25],"rabbit":[27],"muscle":[28],"SERCA1a":[29],"in":[30,67,131,141,165,220,256,267,270,284],"Ca2+/E1":[32],"(E1)":[33],"TG/E2":[35],"(E2)":[36],"conformations,":[37],"we":[38],"performed":[39,246],"computational":[40],"docking":[41,90],"studies":[42],"to":[43,128,168,209,288],"characterize":[44],"molecular":[46,156],"interactions":[47,106],"that":[48,104,121,210],"govern":[49],"binding":[50,79,114,143,149,166,205,222,228],"TG":[52,74,113,136,159,190,268],"TG-analogs":[54],"by":[55,115],"enzyme.":[57,198],"Using":[58],"program":[60],"GOLD":[61],"(genetic":[62],"optimization":[63],"for":[64,183,279],"ligand":[65],"docking)":[66],"combination":[68],"with":[69,98,234,247],"scoring":[71],"function":[72],"ChemScore,":[73],"was":[75,119,244,276],"docked":[76,188],"into":[77,177,192],"site":[80],"E1":[83,129,179],"E2":[85,127,170,194],"conformations":[86],"SERCA1a.":[88],"The":[89,263],"results":[91],"revealed":[92],"consensus":[94],"ligand-binding":[95],"mode":[96,206],"consistent":[97],"structure":[101],"showed":[103,230],"hydrophobic":[105],"are":[107],"primary":[109],"driving":[110],"force":[111],"SERCA.":[116],"Moreover,":[117],"it":[118,174],"shown":[120],"conformational":[123],"changes":[124],"accompanying":[125],"transition":[130],"enzyme":[133],"likely":[134],"displace":[135],"from":[137,175],"its":[138,148,162,178],"favored":[139],"orientation":[140,219],"site,":[144],"thereby":[145],"substantially":[146],"reducing":[147],"affinity.":[150],"This":[151],"finding":[152],"illustrates":[153],"level":[157],"how":[158],"may":[160],"exert":[161],"inhibitory":[163,238],"effect":[164],"tightly":[167],"form":[171],"preventing":[173],"converting":[176],"form,":[180],"requirement":[182],"catalytic":[184],"function.":[185],"We":[186],"also":[187,245],"9":[189],"analogs":[191,202],"conformation":[195],"Eight":[199],"adopted":[203],"very":[207],"similar":[208],"TG,":[212],"whereas":[213],"one":[214],"compound":[215],"preferred":[216],"different":[218],"site.":[223],"Analysis":[224],"predicted":[227],"affinities":[229],"good":[232],"correlation":[233],"experimentally":[236,264],"observed":[237,265],"potencies":[239],"analogs.":[242],"Docking":[243],"several":[248],"modeled":[249],"mutants":[250,275],"SERCA1a,":[252],"whose":[253],"phenylalanine":[254],"residue":[255],"position":[257],"256":[258],"(Phe256)":[259],"had":[260],"been":[261],"modified.":[262],"declines":[266],"sensitivity":[269],"most":[271],"Phe256":[274],"qualitatively":[277],"accounted":[278],"appears,":[281],"at":[282],"least":[283],"part,":[285],"be":[286],"due":[287],"slightly":[290],"altered":[291],"TG-binding":[292],"mode.":[293]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1},{"year":2023,"cited_by_count":1},{"year":2021,"cited_by_count":1},{"year":2019,"cited_by_count":2},{"year":2015,"cited_by_count":1},{"year":2013,"cited_by_count":3},{"year":2012,"cited_by_count":3}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}
