{"id":"https://openalex.org/W4404792205","doi":"https://doi.org/10.1021/acs.biochem.4c00645","title":"Dissecting the Roles of Electrostatic Interactions in Modulating the Folding Stability and Cooperativity of Engrailed Homeodomain","display_name":"Dissecting the Roles of Electrostatic Interactions in Modulating the Folding Stability and Cooperativity of Engrailed Homeodomain","publication_year":2024,"publication_date":"2024-11-27","ids":{"openalex":"https://openalex.org/W4404792205","doi":"https://doi.org/10.1021/acs.biochem.4c00645","pmid":"https://pubmed.ncbi.nlm.nih.gov/39602187"},"language":"en","primary_location":{"id":"doi:10.1021/acs.biochem.4c00645","doi":"https://doi.org/10.1021/acs.biochem.4c00645","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.biochem.4c00645","pdf_url":null,"source":{"id":"https://openalex.org/S104038378","display_name":"Biochemistry","issn_l":"0006-2960","issn":["0006-2960","1520-4995","1943-295X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2"],"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":"Biochemistry","raw_type":"journal-article"},"parent_works":[],"lineage":["https://openalex.org/W4404792205"],"child_works_count":0,"type":"article","is_traditional":true,"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/A5075354732","display_name":"Chengzhen Xu","orcid":"https://orcid.org/0000-0003-3458-9493","observed_orcids":["https://orcid.org/0000-0003-3458-9493"]},"institutions":[{"id":"https://openalex.org/I4405261251","display_name":"The Hong Kong University of Science and Technology (Guangzhou)","ror":"https://ror.org/050h0vm43","country_code":"CN","type":"education","lineage":["https://openalex.org/I4405261251"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Chengzhen Xu","raw_affiliation_strings":["Advanced Materials Thrust, Function Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511400, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Advanced Materials Thrust, Function Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511400, China","institution_ids":["https://openalex.org/I4405261251"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5072626733","display_name":"Xiakun Chu","orcid":"https://orcid.org/0000-0003-3166-7070","observed_orcids":["https://orcid.org/0000-0003-3166-7070"]},"institutions":[{"id":"https://openalex.org/I200769079","display_name":"Hong Kong University of Science and Technology","ror":"https://ror.org/00q4vv597","country_code":"HK","type":"education","lineage":["https://openalex.org/I200769079"]},{"id":"https://openalex.org/I4405261251","display_name":"The Hong Kong University of Science and Technology (Guangzhou)","ror":"https://ror.org/050h0vm43","country_code":"CN","type":"education","lineage":["https://openalex.org/I4405261251"]}],"countries":["CN","HK"],"is_corresponding":true,"raw_author_name":"Xiakun Chu","raw_affiliation_strings":["Advanced Materials Thrust, Function Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511400, China","Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR 999077, China","Guangzhou Municipal Key Laboratory of Materials Informatics, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511400, China"],"raw_orcid":"https://orcid.org/0000-0003-3166-7070","affiliations":[{"raw_affiliation_string":"Advanced Materials Thrust, Function Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511400, China","institution_ids":["https://openalex.org/I4405261251"]},{"raw_affiliation_string":"Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR 999077, China","institution_ids":["https://openalex.org/I200769079"]},{"raw_affiliation_string":"Guangzhou Municipal Key Laboratory of Materials Informatics, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511400, China","institution_ids":["https://openalex.org/I200769079","https://openalex.org/I4405261251"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5072626733"],"corresponding_institution_ids":["https://openalex.org/I200769079","https://openalex.org/I4405261251"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":0.1084,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.29080011,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":93},"biblio":{"volume":"63","issue":"24","first_page":"3261","last_page":"3272"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":1.0,"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":1.0,"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/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.0,"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/T12274","display_name":"Electrostatics and Colloid Interactions","score":0.0,"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/engrailed-homeodomain","display_name":"engrailed homeodomain","score":0.9760000109672546},{"id":"https://openalex.org/keywords/electrostatic-interactions","display_name":"electrostatic interactions","score":0.9539999961853027},{"id":"https://openalex.org/keywords/protein-folding-stability","display_name":"protein folding stability","score":0.8759999871253967},{"id":"https://openalex.org/keywords/cooperative-folding","display_name":"cooperative folding","score":0.9980000257492065},{"id":"https://openalex.org/keywords/salt-effects","display_name":"salt effects","score":0.7680000066757202},{"id":"https://openalex.org/keywords/debye-huckel-theory","display_name":"Debye-H\u00fcckel theory","score":0.9070000052452087},{"id":"https://openalex.org/keywords/two-state-folding","display_name":"two-state folding","score":0.7250000238418579},{"id":"https://openalex.org/keywords/protein-dna-interactions","display_name":"protein-DNA interactions","score":0.5799999833106995},{"id":"https://openalex.org/keywords/transcription-factors","display_name":"transcription factors","score":0.40700000524520874}],"concepts":[{"id":"https://openalex.org/C166014724","wikidata":"https://www.wikidata.org/wiki/Q337217","display_name":"Cooperativity","level":2,"score":0.8227476477622986},{"id":"https://openalex.org/C64632358","wikidata":"https://www.wikidata.org/wiki/Q95351881","display_name":"engrailed","level":5,"score":0.6364468932151794},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6096750497817993},{"id":"https://openalex.org/C117626034","wikidata":"https://www.wikidata.org/wiki/Q26336","display_name":"Electrostatics","level":2,"score":0.6065494418144226},{"id":"https://openalex.org/C159467904","wikidata":"https://www.wikidata.org/wiki/Q2001702","display_name":"Chemical physics","level":1,"score":0.604362428188324},{"id":"https://openalex.org/C2776545253","wikidata":"https://www.wikidata.org/wiki/Q5464292","display_name":"Folding (DSP implementation)","level":2,"score":0.5874594449996948},{"id":"https://openalex.org/C204328495","wikidata":"https://www.wikidata.org/wiki/Q847556","display_name":"Protein folding","level":2,"score":0.5765601396560669},{"id":"https://openalex.org/C87716614","wikidata":"https://www.wikidata.org/wiki/Q845744","display_name":"Static electricity","level":2,"score":0.5635700821876526},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.5437080264091492},{"id":"https://openalex.org/C19472624","wikidata":"https://www.wikidata.org/wiki/Q583851","display_name":"Native state","level":2,"score":0.5192961096763611},{"id":"https://openalex.org/C119621388","wikidata":"https://www.wikidata.org/wiki/Q5377166","display_name":"Energy landscape","level":2,"score":0.46582457423210144},{"id":"https://openalex.org/C206276672","wikidata":"https://www.wikidata.org/wiki/Q5164839","display_name":"Contact order","level":3,"score":0.4130808115005493},{"id":"https://openalex.org/C8010536","wikidata":"https://www.wikidata.org/wiki/Q160398","display_name":"Crystallography","level":1,"score":0.331948459148407},{"id":"https://openalex.org/C121587040","wikidata":"https://www.wikidata.org/wiki/Q898769","display_name":"Homeobox","level":4,"score":0.1713150143623352},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.16819682717323303},{"id":"https://openalex.org/C86339819","wikidata":"https://www.wikidata.org/wiki/Q407384","display_name":"Transcription factor","level":3,"score":0.11577105522155762},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.09976673126220703},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.09396561980247498},{"id":"https://openalex.org/C147789679","wikidata":"https://www.wikidata.org/wiki/Q11372","display_name":"Physical chemistry","level":1,"score":0.06928080320358276},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.0},{"id":"https://openalex.org/C62520636","wikidata":"https://www.wikidata.org/wiki/Q944","display_name":"Quantum mechanics","level":1,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0},{"id":"https://openalex.org/C119599485","wikidata":"https://www.wikidata.org/wiki/Q43035","display_name":"Electrical engineering","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D012492","descriptor_name":"Salts","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":"D014157","descriptor_name":"Transcription Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017510","descriptor_name":"Protein Folding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D018398","descriptor_name":"Homeodomain Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D018398","descriptor_name":"Homeodomain Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D055550","descriptor_name":"Protein Stability","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055672","descriptor_name":"Static Electricity","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}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.biochem.4c00645","doi":"https://doi.org/10.1021/acs.biochem.4c00645","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.biochem.4c00645","pdf_url":null,"source":{"id":"https://openalex.org/S104038378","display_name":"Biochemistry","issn_l":"0006-2960","issn":["0006-2960","1520-4995","1943-295X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2"],"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":"Biochemistry","raw_type":"journal-article"},{"id":"pmid:39602187","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/39602187","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":"Biochemistry","raw_type":"Journal Article"},{"id":"pmh:oai:repository.hkust.edu.hk:1783.1-147070","doi":null,"is_oa":false,"landing_page_url":"http://repository.hkust.edu.hk/ir/Record/1783.1-147070","pdf_url":null,"source":{"id":"https://openalex.org/S4306401796","display_name":"Rare & Special e-Zone (The Hong Kong University of Science and Technology)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I200769079","host_organization_name":"Hong Kong University of Science and Technology","host_organization_lineage":["https://openalex.org/I200769079"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Article"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G1101147792","display_name":null,"funder_award_id":"2023A03J0060","funder_id":"https://openalex.org/F4320335480","funder_display_name":"Guangzhou Municipal Science and Technology Project"},{"id":"https://openalex.org/G1966227882","display_name":null,"funder_award_id":"32201020","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"},{"id":"https://openalex.org/G3833593571","display_name":null,"funder_award_id":"2024A1515010862","funder_id":"https://openalex.org/F4320337111","funder_display_name":"Basic and Applied Basic Research Foundation of Guangdong Province"},{"id":"https://openalex.org/G7020882947","display_name":null,"funder_award_id":"2023A03J0003","funder_id":"https://openalex.org/F4320335480","funder_display_name":"Guangzhou Municipal Science and Technology Project"},{"id":"https://openalex.org/G7267843516","display_name":null,"funder_award_id":"12474201","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"},{"id":"https://openalex.org/G8049540444","display_name":null,"funder_award_id":"2023KTSCX169","funder_id":"https://openalex.org/F4320326279","funder_display_name":"Department of Education of Guangdong Province"},{"id":"https://openalex.org/G8110914009","display_name":null,"funder_award_id":"2023A04J0083","funder_id":"https://openalex.org/F4320335480","funder_display_name":"Guangzhou Municipal Science and Technology Project"}],"funders":[{"id":"https://openalex.org/F4320321001","display_name":"National Natural Science Foundation of China","ror":"https://ror.org/01h0zpd94"},{"id":"https://openalex.org/F4320326279","display_name":"Department of Education of Guangdong Province","ror":"https://ror.org/01s5gyw91"},{"id":"https://openalex.org/F4320335480","display_name":"Guangzhou Municipal Science and Technology Project","ror":null},{"id":"https://openalex.org/F4320337111","display_name":"Basic and Applied Basic Research Foundation of Guangdong Province","ror":null}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":74,"referenced_works":["https://openalex.org/W1566565124","https://openalex.org/W1966078827","https://openalex.org/W1968237188","https://openalex.org/W1973349921","https://openalex.org/W1973667581","https://openalex.org/W1976528962","https://openalex.org/W1978033776","https://openalex.org/W1979018519","https://openalex.org/W1980881525","https://openalex.org/W1981369098","https://openalex.org/W1985581386","https://openalex.org/W1988690429","https://openalex.org/W1991252112","https://openalex.org/W1994840640","https://openalex.org/W1995312720","https://openalex.org/W2011246315","https://openalex.org/W2012092107","https://openalex.org/W2023231003","https://openalex.org/W2023391815","https://openalex.org/W2032107762","https://openalex.org/W2032311486","https://openalex.org/W2040809566","https://openalex.org/W2046290651","https://openalex.org/W2053111993","https://openalex.org/W2053960740","https://openalex.org/W2055982953","https://openalex.org/W2059490112","https://openalex.org/W2065023288","https://openalex.org/W2065864578","https://openalex.org/W2067236515","https://openalex.org/W2069662497","https://openalex.org/W2070783701","https://openalex.org/W2071522549","https://openalex.org/W2073978055","https://openalex.org/W2076849893","https://openalex.org/W2079492386","https://openalex.org/W2079536614","https://openalex.org/W2083939457","https://openalex.org/W2088780328","https://openalex.org/W2092356013","https://openalex.org/W2097054029","https://openalex.org/W2098106418","https://openalex.org/W2102074396","https://openalex.org/W2105632084","https://openalex.org/W2108107378","https://openalex.org/W2109978487","https://openalex.org/W2112154906","https://openalex.org/W2115273980","https://openalex.org/W2120094698","https://openalex.org/W2123768455","https://openalex.org/W2127184995","https://openalex.org/W2137712029","https://openalex.org/W2140565568","https://openalex.org/W2140918987","https://openalex.org/W2144562104","https://openalex.org/W2145326890","https://openalex.org/W2165414288","https://openalex.org/W2171755502","https://openalex.org/W2266488717","https://openalex.org/W2330799739","https://openalex.org/W2332891016","https://openalex.org/W2440693113","https://openalex.org/W2517371615","https://openalex.org/W2613247437","https://openalex.org/W2620727311","https://openalex.org/W2765357343","https://openalex.org/W2884206968","https://openalex.org/W3003808794","https://openalex.org/W3092975235","https://openalex.org/W4200171943","https://openalex.org/W4205991643","https://openalex.org/W4220760286","https://openalex.org/W4398197849","https://openalex.org/W4402557848"],"related_works":["https://openalex.org/W1981369098","https://openalex.org/W1980881525","https://openalex.org/W4416383909","https://openalex.org/W4361276824","https://openalex.org/W2064416558","https://openalex.org/W2049599330","https://openalex.org/W2320736505","https://openalex.org/W2008976260","https://openalex.org/W1263807564","https://openalex.org/W1970454323"],"abstract_inverted_index":{"Engrailed":[0],"homeodomain":[1],"(EngHD),":[2],"a":[3,13,59,127,131,137,169],"highly":[4,213],"charged":[5,23,214],"transcription":[6],"factor":[7],"regulating":[8],"over":[9],"200":[10],"genes,":[11],"is":[12],"fast-folding":[14],"protein.":[15],"Recent":[16],"studies":[17],"have":[18],"shown":[19],"that":[20,63,83],"the":[21,35,43,50,65,71,94,103,112,122,141,155,161,174,184,202,208],"abundant":[22],"residues":[24],"in":[25,160,173],"EngHD":[26,53,75,125],"not":[27],"only":[28],"facilitate":[29],"protein-DNA":[30],"interactions":[31,48,145,158,200],"but":[32],"also":[33],"influence":[34,201],"conformational":[36],"disorder":[37],"of":[38,52,74,124,143,164,176,187,204],"its":[39],"native":[40,162],"structure.":[41],"However,":[42],"mechanisms":[44],"by":[45,183],"which":[46],"electrostatic":[47,105,157,199],"modulate":[49],"folding":[51,89,95,123,177,203],"remain":[54],"unclear.":[55],"Here,":[56],"we":[57,120,135,167],"employ":[58],"coarse-grained":[60],"structure-based":[61],"model":[62,68],"incorporates":[64],"salt-dependent":[66],"Debye-H\u00fcckel":[67],"to":[69,102,130,154,207],"investigate":[70],"(un)folding":[72],"behavior":[73],"under":[76],"various":[77],"salt":[78,85,180],"concentrations.":[79],"Our":[80,192],"findings":[81],"demonstrate":[82],"increasing":[84],"concentrations":[86],"enhance":[87],"both":[88],"stability":[90],"and":[91,117,146,189],"cooperativity,":[92],"while":[93],"barrier":[96],"height":[97],"remains":[98],"relatively":[99],"constant":[100],"due":[101],"distinct":[104],"effects":[106],"on":[107,179],"individual":[108],"residues.":[109],"By":[110],"modulating":[111],"energetic":[113,185],"balance":[114,186],"between":[115,140],"local":[116,144,188],"nonlocal":[118,190],"interactions,":[119],"shift":[121],"from":[126],"downhill":[128],"process":[129],"two-state":[132],"process.":[133],"Notably,":[134],"observe":[136],"nonmonotonic":[138],"relationship":[139],"strength":[142],"residue-level":[147],"coupling":[148],"degree":[149],"during":[150],"(un)folding,":[151],"likely":[152],"attributed":[153],"repulsive":[156],"present":[159],"structure":[163],"EngHD.":[165],"Additionally,":[166],"identify":[168],"critical":[170],"turning":[171],"point":[172],"dependence":[175],"cooperativity":[178],"concentration,":[181],"classified":[182],"interactions.":[191],"results":[193],"provide":[194],"valuable":[195],"insights":[196],"into":[197],"how":[198],"EngHD,":[205],"contributing":[206],"theoretical":[209],"framework":[210],"for":[211],"engineering":[212],"proteins.":[215]},"counts_by_year":[{"year":2025,"cited_by_count":1}],"updated_date":"2026-11-13T13:42:25.865203","created_date":"2024-11-28T00:00:00"}