{"id":"https://openalex.org/W2129182459","doi":"https://doi.org/10.1073/pnas.1303930110","title":"Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors","display_name":"Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors","publication_year":2013,"publication_date":"2013-06-24","ids":{"openalex":"https://openalex.org/W2129182459","doi":"https://doi.org/10.1073/pnas.1303930110","mag":"2129182459","pmid":"https://pubmed.ncbi.nlm.nih.gov/23798447","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/3710831"},"language":"en","primary_location":{"id":"doi:10.1073/pnas.1303930110","doi":"https://doi.org/10.1073/pnas.1303930110","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.1303930110","pdf_url":"https://www.pnas.org/content/pnas/110/28/11475.full.pdf","source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://www.pnas.org/content/pnas/110/28/11475.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5048475119","display_name":"Michael J. Harms","orcid":"https://orcid.org/0000-0002-0241-4122","observed_orcids":["https://orcid.org/0000-0002-0241-4122"]},"institutions":[{"id":"https://openalex.org/I181233156","display_name":"University of Oregon","ror":"https://ror.org/0293rh119","country_code":"US","type":"education","lineage":["https://openalex.org/I181233156"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael J. Harms","raw_affiliation_strings":["Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403;","Institute of Ecology and Evolution, University of Oregon, Eugene, OR, 97403, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403;","institution_ids":["https://openalex.org/I181233156"]},{"raw_affiliation_string":"Institute of Ecology and Evolution, University of Oregon, Eugene, OR, 97403, USA","institution_ids":["https://openalex.org/I181233156"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5015054764","display_name":"Geeta N. Eick","orcid":"https://orcid.org/0000-0001-7512-3265","observed_orcids":["https://orcid.org/0000-0001-7512-3265"]},"institutions":[{"id":"https://openalex.org/I181233156","display_name":"University of Oregon","ror":"https://ror.org/0293rh119","country_code":"US","type":"education","lineage":["https://openalex.org/I181233156"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Geeta N. Eick","raw_affiliation_strings":["Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403;","aInstitute of Ecology and Evolution, University of Oregon, Eugene, OR 97403;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403;","institution_ids":["https://openalex.org/I181233156"]},{"raw_affiliation_string":"aInstitute of Ecology and Evolution, University of Oregon, Eugene, OR 97403;","institution_ids":["https://openalex.org/I181233156"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054993193","display_name":"Devrishi Goswami","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I123431417","display_name":"Scripps Research Institute","ror":"https://ror.org/02dxx6824","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I123431417"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Devrishi Goswami","raw_affiliation_strings":["Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458;","bDepartment of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458;","institution_ids":["https://openalex.org/I123431417"]},{"raw_affiliation_string":"bDepartment of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458;","institution_ids":["https://openalex.org/I123431417"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060536807","display_name":"Jennifer K. Colucci","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I150468666","display_name":"Emory University","ror":"https://ror.org/03czfpz43","country_code":"US","type":"education","lineage":["https://openalex.org/I150468666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jennifer K. Colucci","raw_affiliation_strings":["Biochemistry Department, Emory University School of Medicine, Atlanta, GA 30322; and","cBiochemistry Department, Emory University School of Medicine, Atlanta, GA 30322; and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biochemistry Department, Emory University School of Medicine, Atlanta, GA 30322; and","institution_ids":["https://openalex.org/I150468666"]},{"raw_affiliation_string":"cBiochemistry Department, Emory University School of Medicine, Atlanta, GA 30322; and","institution_ids":["https://openalex.org/I150468666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000139914","display_name":"Patrick R. Griffin","orcid":"https://orcid.org/0000-0002-3404-690X","observed_orcids":["https://orcid.org/0000-0002-3404-690X"]},"institutions":[{"id":"https://openalex.org/I123431417","display_name":"Scripps Research Institute","ror":"https://ror.org/02dxx6824","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I123431417"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Patrick R. Griffin","raw_affiliation_strings":["Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458;","bDepartment of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458;","institution_ids":["https://openalex.org/I123431417"]},{"raw_affiliation_string":"bDepartment of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458;","institution_ids":["https://openalex.org/I123431417"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042492247","display_name":"Eric A. Ortlund","orcid":"https://orcid.org/0000-0001-8855-3029","observed_orcids":["https://orcid.org/0000-0001-8855-3029"]},"institutions":[{"id":"https://openalex.org/I150468666","display_name":"Emory University","ror":"https://ror.org/03czfpz43","country_code":"US","type":"education","lineage":["https://openalex.org/I150468666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Eric A. Ortlund","raw_affiliation_strings":["Biochemistry Department, Emory University School of Medicine, Atlanta, GA 30322; and","cBiochemistry Department, Emory University School of Medicine, Atlanta, GA 30322; and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biochemistry Department, Emory University School of Medicine, Atlanta, GA 30322; and","institution_ids":["https://openalex.org/I150468666"]},{"raw_affiliation_string":"cBiochemistry Department, Emory University School of Medicine, Atlanta, GA 30322; and","institution_ids":["https://openalex.org/I150468666"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5026537989","display_name":"Joseph W. Thornton","orcid":"https://orcid.org/0000-0001-9589-6994","observed_orcids":["https://orcid.org/0000-0001-9589-6994"]},"institutions":[{"id":"https://openalex.org/I181233156","display_name":"University of Oregon","ror":"https://ror.org/0293rh119","country_code":"US","type":"education","lineage":["https://openalex.org/I181233156"]},{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joseph W. Thornton","raw_affiliation_strings":["Departments of Human Genetics and Ecology and Evolution, The University of Chicago, Chicago, IL 60637","Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403;","aInstitute of Ecology and Evolution, University of Oregon, Eugene, OR 97403;","dDepartments of Human Genetics and Ecology and Evolution, The University of Chicago, Chicago, IL 60637"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Human Genetics and Ecology and Evolution, The University of Chicago, Chicago, IL 60637","institution_ids":["https://openalex.org/I40347166"]},{"raw_affiliation_string":"Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403;","institution_ids":["https://openalex.org/I181233156"]},{"raw_affiliation_string":"aInstitute of Ecology and Evolution, University of Oregon, Eugene, OR 97403;","institution_ids":["https://openalex.org/I181233156"]},{"raw_affiliation_string":"dDepartments of Human Genetics and Ecology and Evolution, The University of Chicago, Chicago, IL 60637","institution_ids":["https://openalex.org/I40347166"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":4.52,"has_fulltext":true,"cited_by_count":72,"citation_normalized_percentile":{"value":0.96277655,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":90,"max":100},"biblio":{"volume":"110","issue":"28","first_page":"11475","last_page":"11480"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9262999892234802,"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":0.9262999892234802,"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/T10756","display_name":"Estrogen and related hormone effects","score":0.029100000858306885,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/T11764","display_name":"Evolution and Genetic Dynamics","score":0.026100000366568565,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/steroid-hormone-receptors","display_name":"steroid hormone receptors","score":0.9950000047683716},{"id":"https://openalex.org/keywords/protein-function-evolution","display_name":"protein function evolution","score":0.6159999966621399},{"id":"https://openalex.org/keywords/ligand-specificity","display_name":"ligand specificity","score":0.7559999823570251},{"id":"https://openalex.org/keywords/ancestral-protein-reconstruction","display_name":"ancestral protein reconstruction","score":0.8169999718666077},{"id":"https://openalex.org/keywords/estrogen-sensitivity","display_name":"estrogen sensitivity","score":0.7710000276565552},{"id":"https://openalex.org/keywords/androgen-sensitivity","display_name":"androgen sensitivity","score":0.6650000214576721},{"id":"https://openalex.org/keywords/hydrogen-bond-network","display_name":"hydrogen bond network","score":0.7269999980926514},{"id":"https://openalex.org/keywords/protein-dynamics","display_name":"protein dynamics","score":0.8550000190734863},{"id":"https://openalex.org/keywords/transcription-factors","display_name":"transcription factors","score":0.492000013589859},{"id":"https://openalex.org/keywords/amino-acid-substitutions","display_name":"amino acid substitutions","score":0.5400000214576721}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6244632601737976},{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.5572437047958374},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.5113570094108582},{"id":"https://openalex.org/C2780902042","wikidata":"https://www.wikidata.org/wiki/Q177911","display_name":"Steroid","level":3,"score":0.4767128825187683},{"id":"https://openalex.org/C84606932","wikidata":"https://www.wikidata.org/wiki/Q416496","display_name":"Estrogen receptor","level":4,"score":0.466778427362442},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.46114689111709595},{"id":"https://openalex.org/C2776888042","wikidata":"https://www.wikidata.org/wiki/Q422137","display_name":"Steroid hormone","level":3,"score":0.45216381549835205},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.4433349370956421},{"id":"https://openalex.org/C71315377","wikidata":"https://www.wikidata.org/wiki/Q11364","display_name":"Hormone","level":2,"score":0.3559655249118805},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.28743427991867065},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.0},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D001703","descriptor_name":"Biophysics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008024","descriptor_name":"Ligands","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":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D010802","descriptor_name":"Phylogeny","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":"D011987","descriptor_name":"Receptors, Steroid","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D011987","descriptor_name":"Receptors, Steroid","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011987","descriptor_name":"Receptors, Steroid","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D019143","descriptor_name":"Evolution, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":4,"locations":[{"id":"doi:10.1073/pnas.1303930110","doi":"https://doi.org/10.1073/pnas.1303930110","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.1303930110","pdf_url":"https://www.pnas.org/content/pnas/110/28/11475.full.pdf","source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},{"id":"pmh:oai:europepmc.org:2871455","doi":null,"is_oa":true,"landing_page_url":"http://europepmc.org/articles/PMC3710831","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"","raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:3710831","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3710831","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"Proc Natl Acad Sci U S A","raw_type":"Text"},{"id":"pmid:23798447","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/23798447","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":"Proceedings of the National Academy of Sciences of the United States of America","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1073/pnas.1303930110","doi":"https://doi.org/10.1073/pnas.1303930110","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.1303930110","pdf_url":"https://www.pnas.org/content/pnas/110/28/11475.full.pdf","source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G1568165062","display_name":"Mixed-Model Phylogenetic Methods for Evolutionarily Heterogeneous Data","funder_award_id":"0516530","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G3100368705","display_name":"Experimental and structural evolution of hormone receptors","funder_award_id":"R01GM081592","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G5489267745","display_name":"Molecular Mechanisms of the Evolution of Steroid Receptor-Ligand Interactions","funder_award_id":"F32GM090650","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G587475685","display_name":"CAREER: Molecular Evolution of Steroid Hormone Receptor Function And Interactions","funder_award_id":"0546906","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G6433172018","display_name":"Acquisition of a LTQ/Orbitrap MS to advance the study of protein dynamics","funder_award_id":"S10RR027270","funder_id":"https://openalex.org/F4320337375","funder_display_name":"National Center for Research Resources"},{"id":"https://openalex.org/G6494722911","display_name":"Mechanisms for the evolution of novel DNA specificity in a transcription factor f","funder_award_id":"R01GM104397","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"}],"funders":[{"id":"https://openalex.org/F4320306076","display_name":"National Science Foundation","ror":"https://ror.org/021nxhr62"},{"id":"https://openalex.org/F4320306082","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"},{"id":"https://openalex.org/F4320337375","display_name":"National Center for Research Resources","ror":"https://ror.org/04pw6fb54"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2129182459.pdf","grobid_xml":"https://content.openalex.org/works/W2129182459.grobid-xml"},"referenced_works_count":25,"referenced_works":["https://openalex.org/W1509876279","https://openalex.org/W1516034258","https://openalex.org/W1983057459","https://openalex.org/W1985023530","https://openalex.org/W1997116773","https://openalex.org/W2002090103","https://openalex.org/W2006964552","https://openalex.org/W2027351435","https://openalex.org/W2031598022","https://openalex.org/W2062210712","https://openalex.org/W2070815451","https://openalex.org/W2077564233","https://openalex.org/W2084550263","https://openalex.org/W2088012478","https://openalex.org/W2096344315","https://openalex.org/W2098448352","https://openalex.org/W2102795115","https://openalex.org/W2104093308","https://openalex.org/W2115570685","https://openalex.org/W2116474322","https://openalex.org/W2122449403","https://openalex.org/W2123653059","https://openalex.org/W2127522551","https://openalex.org/W2131918208","https://openalex.org/W2171268876"],"related_works":["https://openalex.org/W3184884485","https://openalex.org/W2031598022","https://openalex.org/W2071461674","https://openalex.org/W1998947682","https://openalex.org/W2994215628","https://openalex.org/W2086941051","https://openalex.org/W2002290225","https://openalex.org/W2488369101","https://openalex.org/W2155762441","https://openalex.org/W3174384633"],"abstract_inverted_index":{"The":[0],"genetic":[1,57],"and":[2,19,59,65,71,117,192,209],"biophysical":[3],"mechanisms":[4,45],"by":[5,33,130,162],"which":[6,136],"new":[7],"protein":[8,29,54,63],"functions":[9],"evolve":[10],"is":[11,24],"a":[12,34,81,138,174,198],"central":[13],"question":[14],"in":[15,28,74,77,125,141,206],"evolutionary":[16],"biology,":[17],"biochemistry,":[18],"biophysics.":[20],"Of":[21],"particular":[22],"interest":[23],"whether":[25],"major":[26,204],"shifts":[27,205],"function":[30,126,210],"are":[31],"caused":[32,137],"few":[35,199],"mutations":[36,202],"of":[37,62,83,95,152,166,177,211],"large":[38],"effect":[39],"and,":[40],"if":[41],"they":[42,157],"are,":[43],"the":[44,78,93,96,142,150,170,189,207,212],"that":[46,92,122],"mediate":[47],"these":[48],"changes.":[49],"Here":[50,119],"we":[51,120],"combine":[52],"ancestral":[53,143],"reconstruction":[55],"with":[56],"manipulation":[58],"explicit":[60],"studies":[61],"structure":[64],"dynamics":[66,193],"to":[67,114,183],"dissect":[68],"an":[69,164],"ancient":[70],"discrete":[72],"shift":[73,124],"ligand":[75],"specificity":[76],"steroid":[79,98],"receptors,":[80],"family":[82,100],"biologically":[84],"essential":[85],"hormone-controlled":[86],"transcription":[87],"factors.":[88],"We":[89],"previously":[90],"found":[91],"ancestor":[94],"entire":[97],"receptor":[99],"was":[101,111,127],"highly":[102],"specific":[103],"for":[104],"estrogens,":[105],"but":[106,156],"its":[107,195],"immediate":[108],"phylogenetic":[109],"descendant":[110],"sensitive":[112],"only":[113],"androgens,":[115],"progestogens,":[116],"corticosteroids.":[118],"show":[121],"this":[123],"driven":[128],"primarily":[129],"two":[131,153],"historical":[132],"amino":[133,154],"acid":[134],"changes,":[135],"\u223c70,000-fold":[139],"change":[140],"protein's":[144,190],"specificity.":[145],"These":[146],"replacements":[147],"subtly":[148],"changed":[149],"chemistry":[151],"acids,":[155],"dramatically":[158],"reduced":[159],"estrogen":[160],"sensitivity":[161],"introducing":[163],"excess":[165],"interaction":[167],"partners":[168],"into":[169,203],"receptor/estrogen":[171],"complex,":[172],"inducing":[173],"frustrated":[175],"ensemble":[176],"suboptimal":[178],"hydrogen":[179],"bond":[180],"networks":[181],"unique":[182],"estrogens.":[184],"This":[185],"work":[186],"shows":[187],"how":[188],"architecture":[191],"shaped":[194],"evolution,":[196],"amplifying":[197],"biochemically":[200],"subtle":[201],"energetics":[208],"protein.":[213]},"counts_by_year":[{"year":2026,"cited_by_count":3},{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":3},{"year":2023,"cited_by_count":6},{"year":2022,"cited_by_count":4},{"year":2021,"cited_by_count":5},{"year":2020,"cited_by_count":3},{"year":2018,"cited_by_count":3},{"year":2017,"cited_by_count":8},{"year":2016,"cited_by_count":9},{"year":2015,"cited_by_count":7},{"year":2014,"cited_by_count":16},{"year":2013,"cited_by_count":4}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}