{"id":"https://openalex.org/W3164821738","doi":"https://doi.org/10.1021/acs.jcim.1c00419","title":"Adaptative Steered Molecular Dynamics Study of Mutagenesis Effects on Calcium Affinity in the Regulatory Domain of Cardiac Troponin C","display_name":"Adaptative Steered Molecular Dynamics Study of Mutagenesis Effects on Calcium Affinity in the Regulatory Domain of Cardiac Troponin C","publication_year":2021,"publication_date":"2021-06-03","ids":{"openalex":"https://openalex.org/W3164821738","doi":"https://doi.org/10.1021/acs.jcim.1c00419","mag":"3164821738","pmid":"https://pubmed.ncbi.nlm.nih.gov/34080877"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.1c00419","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.1c00419","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":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8350873","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5085010994","display_name":"Eric R. Hantz","orcid":"https://orcid.org/0000-0002-2588-7619"},"institutions":[{"id":"https://openalex.org/I52357470","display_name":"The Ohio State University","ror":"https://ror.org/00rs6vg23","country_code":"US","type":"education","lineage":["https://openalex.org/I52357470"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Eric R. Hantz","raw_affiliation_strings":["Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States"],"raw_orcid":"https://orcid.org/0000-0002-2588-7619","affiliations":[{"raw_affiliation_string":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States","institution_ids":["https://openalex.org/I52357470"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5044975181","display_name":"Steffen Lindert","orcid":"https://orcid.org/0000-0002-3976-3473"},"institutions":[{"id":"https://openalex.org/I52357470","display_name":"The Ohio State University","ror":"https://ror.org/00rs6vg23","country_code":"US","type":"education","lineage":["https://openalex.org/I52357470"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Steffen Lindert","raw_affiliation_strings":["Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States"],"raw_orcid":"https://orcid.org/0000-0002-3976-3473","affiliations":[{"raw_affiliation_string":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States","institution_ids":["https://openalex.org/I52357470"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5044975181"],"corresponding_institution_ids":["https://openalex.org/I52357470"],"apc_list":null,"apc_paid":null,"fwci":1.7481,"has_fulltext":false,"cited_by_count":14,"citation_normalized_percentile":{"value":0.85952474,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":91,"max":99},"biblio":{"volume":"61","issue":"6","first_page":"3052","last_page":"3057"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10882","display_name":"Cardiomyopathy and Myosin Studies","score":0.9965999722480774,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10882","display_name":"Cardiomyopathy and Myosin Studies","score":0.9965999722480774,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.9950000047683716,"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/T10044","display_name":"Protein Structure and Dynamics","score":0.9850000143051147,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/troponin-c","display_name":"Troponin C","score":0.7460078001022339},{"id":"https://openalex.org/keywords/calcium","display_name":"Calcium","score":0.6183362603187561},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.606083869934082},{"id":"https://openalex.org/keywords/contractility","display_name":"Contractility","score":0.5610114336013794},{"id":"https://openalex.org/keywords/biophysics","display_name":"Biophysics","score":0.539309024810791},{"id":"https://openalex.org/keywords/mutagenesis","display_name":"Mutagenesis","score":0.5228172540664673},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.5001785755157471},{"id":"https://openalex.org/keywords/binding-site","display_name":"Binding site","score":0.4649459421634674},{"id":"https://openalex.org/keywords/mutant","display_name":"Mutant","score":0.4478845000267029},{"id":"https://openalex.org/keywords/binding-domain","display_name":"Binding domain","score":0.4287504553794861},{"id":"https://openalex.org/keywords/troponin","display_name":"Troponin","score":0.4078243374824524},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.34191954135894775},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.3341057598590851},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.2704888880252838},{"id":"https://openalex.org/keywords/gene","display_name":"Gene","score":0.14270144701004028},{"id":"https://openalex.org/keywords/cardiology","display_name":"Cardiology","score":0.11207336187362671},{"id":"https://openalex.org/keywords/medicine","display_name":"Medicine","score":0.1060093343257904},{"id":"https://openalex.org/keywords/endocrinology","display_name":"Endocrinology","score":0.07800933718681335},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.07349935173988342}],"concepts":[{"id":"https://openalex.org/C133927893","wikidata":"https://www.wikidata.org/wiki/Q4383200","display_name":"Troponin C","level":4,"score":0.7460078001022339},{"id":"https://openalex.org/C519063684","wikidata":"https://www.wikidata.org/wiki/Q706","display_name":"Calcium","level":2,"score":0.6183362603187561},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.606083869934082},{"id":"https://openalex.org/C39133596","wikidata":"https://www.wikidata.org/wiki/Q5165683","display_name":"Contractility","level":2,"score":0.5610114336013794},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.539309024810791},{"id":"https://openalex.org/C16318435","wikidata":"https://www.wikidata.org/wiki/Q149299","display_name":"Mutagenesis","level":4,"score":0.5228172540664673},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5001785755157471},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.4649459421634674},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.4478845000267029},{"id":"https://openalex.org/C25166345","wikidata":"https://www.wikidata.org/wiki/Q4914012","display_name":"Binding domain","level":3,"score":0.4287504553794861},{"id":"https://openalex.org/C36036425","wikidata":"https://www.wikidata.org/wiki/Q7846262","display_name":"Troponin","level":3,"score":0.4078243374824524},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.34191954135894775},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3341057598590851},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2704888880252838},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.14270144701004028},{"id":"https://openalex.org/C164705383","wikidata":"https://www.wikidata.org/wiki/Q10379","display_name":"Cardiology","level":1,"score":0.11207336187362671},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.1060093343257904},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.07800933718681335},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.07349935173988342},{"id":"https://openalex.org/C500558357","wikidata":"https://www.wikidata.org/wiki/Q12152","display_name":"Myocardial infarction","level":2,"score":0.0},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D002118","descriptor_name":"Calcium","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002118","descriptor_name":"Calcium","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002118","descriptor_name":"Calcium","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D009206","descriptor_name":"Myocardium","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D009206","descriptor_name":"Myocardium","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D009206","descriptor_name":"Myocardium","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D016296","descriptor_name":"Mutagenesis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016296","descriptor_name":"Mutagenesis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016296","descriptor_name":"Mutagenesis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019209","descriptor_name":"Troponin C","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D019209","descriptor_name":"Troponin C","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D019209","descriptor_name":"Troponin C","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D019209","descriptor_name":"Troponin C","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019209","descriptor_name":"Troponin C","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019209","descriptor_name":"Troponin C","qualifier_ui":"Q000378","qualifier_name":"metabolism","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},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.1c00419","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.1c00419","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:34080877","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/34080877","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},{"id":"pmh:oai:pubmedcentral.nih.gov:8350873","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8350873","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,"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":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:8350873","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8350873","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,"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":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.6600000262260437}],"awards":[{"id":"https://openalex.org/G5254454243","display_name":null,"funder_award_id":"R01 HL 137015","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":48,"referenced_works":["https://openalex.org/W196794146","https://openalex.org/W203363010","https://openalex.org/W1062333943","https://openalex.org/W1550330933","https://openalex.org/W1955453661","https://openalex.org/W1971397263","https://openalex.org/W1978159078","https://openalex.org/W1987363474","https://openalex.org/W1994941561","https://openalex.org/W2003530350","https://openalex.org/W2004822259","https://openalex.org/W2013754612","https://openalex.org/W2035266068","https://openalex.org/W2040954790","https://openalex.org/W2080113872","https://openalex.org/W2096163961","https://openalex.org/W2098650992","https://openalex.org/W2103019222","https://openalex.org/W2141011888","https://openalex.org/W2145041436","https://openalex.org/W2149801992","https://openalex.org/W2163058313","https://openalex.org/W2170218133","https://openalex.org/W2172568378","https://openalex.org/W2281888467","https://openalex.org/W2316392160","https://openalex.org/W2320257676","https://openalex.org/W2320380254","https://openalex.org/W2326498796","https://openalex.org/W2332712348","https://openalex.org/W2333047204","https://openalex.org/W2340059643","https://openalex.org/W2345003636","https://openalex.org/W2404280981","https://openalex.org/W2468354249","https://openalex.org/W2469354327","https://openalex.org/W2512614778","https://openalex.org/W2513378292","https://openalex.org/W2617018495","https://openalex.org/W2885824841","https://openalex.org/W2942212357","https://openalex.org/W2946934695","https://openalex.org/W2952635193","https://openalex.org/W2964105050","https://openalex.org/W3080330343","https://openalex.org/W3126168703","https://openalex.org/W4235081531","https://openalex.org/W4236310880"],"related_works":["https://openalex.org/W1999689773","https://openalex.org/W2049996685","https://openalex.org/W2346785564","https://openalex.org/W33325980","https://openalex.org/W1892398115","https://openalex.org/W1748839846","https://openalex.org/W2420862808","https://openalex.org/W1900711230","https://openalex.org/W2462444579","https://openalex.org/W3004814566"],"abstract_inverted_index":{"Calcium-dependent":[0],"cardiac":[1,35],"muscle":[2,36],"contraction":[3],"is":[4,40,132],"regulated":[5],"by":[6,14,42],"the":[7,15,54,63,76,82,96,124,139],"protein":[8],"complex":[9],"troponin":[10],"(cTn)":[11],"and":[12,38,86,111,131,141],"specifically":[13],"regulatory":[16],"N-terminal":[17],"domain":[18],"(N-cTnC)":[19],"which":[20,46],"contains":[21],"one":[22],"active":[23],"Ca2+":[24,125],"binding":[25,49,72,126],"site":[26,69],"(site":[27],"II).":[28],"It":[29],"has":[30],"been":[31],"previously":[32],"shown":[33,103],"that":[34],"contractility":[37],"functionality":[39],"affected":[41],"mutations":[43,67,145],"in":[44,89],"N-cTnC":[45,66,129],"alter":[47],"calcium":[48,71,84],"affinity.":[50,73],"Here,":[51],"we":[52],"describe":[53],"application":[55],"of":[56,65,81,98,128,143],"adaptive":[57],"steered":[58],"molecular":[59],"dynamics":[60],"to":[61,104,121,137],"characterize":[62],"influence":[64],"on":[68],"II":[70,93],"We":[74],"observed":[75],"correct":[77],"trends":[78],"for":[79],"all":[80],"studied":[83],"sensitizing":[85],"desensitizing":[87],"mutants,":[88],"conjunction":[90],"with":[91,107,146],"loop":[92],"perturbations.":[94],"Additionally,":[95],"potential":[97,135,147],"mean":[99],"force":[100],"accuracy":[101],"was":[102],"increase":[105],"substantially":[106],"increasingly":[108],"slower":[109],"speeds":[110],"using":[112],"fewer":[113],"trajectories.":[114],"This":[115],"study":[116],"presents":[117],"a":[118,133],"novel":[119,144],"approach":[120],"computationally":[122],"estimate":[123],"affinity":[127],"structures":[130],"valuable":[134],"tool":[136],"support":[138],"design":[140],"characterization":[142],"therapeutic":[148],"benefits.":[149]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":7}],"updated_date":"2026-05-16T08:24:45.110214","created_date":"2021-06-07T00:00:00"}