{"id":"https://openalex.org/W4414620874","doi":"https://doi.org/10.1021/acs.jcim.5c01255","title":"Molecular Dynamics and Neural Network Analysis Reveal Sequential Gating and Allosteric Communication in FMRFamide-Activated Sodium Channels","display_name":"Molecular Dynamics and Neural Network Analysis Reveal Sequential Gating and Allosteric Communication in FMRFamide-Activated Sodium Channels","publication_year":2025,"publication_date":"2025-09-29","ids":{"openalex":"https://openalex.org/W4414620874","doi":"https://doi.org/10.1021/acs.jcim.5c01255","pmid":"https://pubmed.ncbi.nlm.nih.gov/41022701"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c01255","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c01255","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/A5100671790","display_name":"Jianlin Li","orcid":"https://orcid.org/0000-0002-5267-3931"},"institutions":[{"id":"https://openalex.org/I162868743","display_name":"Tianjin University","ror":"https://ror.org/012tb2g32","country_code":"CN","type":"education","lineage":["https://openalex.org/I162868743"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jianlin Li","raw_affiliation_strings":["Academy of Medical Engineering and Translational Medicine, Medical College","Tianjin University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Academy of Medical Engineering and Translational Medicine, Medical College","institution_ids":[]},{"raw_affiliation_string":"Tianjin University","institution_ids":["https://openalex.org/I162868743"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5031152986","display_name":"Li Lu","orcid":"https://orcid.org/0000-0003-2523-3372"},"institutions":[{"id":"https://openalex.org/I162868743","display_name":"Tianjin University","ror":"https://ror.org/012tb2g32","country_code":"CN","type":"education","lineage":["https://openalex.org/I162868743"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Lu Li","raw_affiliation_strings":["Academy of Medical Engineering and Translational Medicine, Medical College","Tianjin University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Academy of Medical Engineering and Translational Medicine, Medical College","institution_ids":[]},{"raw_affiliation_string":"Tianjin University","institution_ids":["https://openalex.org/I162868743"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002055009","display_name":"Zhiwei Gao","orcid":"https://orcid.org/0000-0001-5464-3288"},"institutions":[{"id":"https://openalex.org/I162868743","display_name":"Tianjin University","ror":"https://ror.org/012tb2g32","country_code":"CN","type":"education","lineage":["https://openalex.org/I162868743"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zhiwei Gao","raw_affiliation_strings":["Academy of Medical Engineering and Translational Medicine, Medical College","Tianjin University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Academy of Medical Engineering and Translational Medicine, Medical College","institution_ids":[]},{"raw_affiliation_string":"Tianjin University","institution_ids":["https://openalex.org/I162868743"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5018630756","display_name":"Yutao Tian","orcid":"https://orcid.org/0000-0002-0622-5070"},"institutions":[{"id":"https://openalex.org/I162868743","display_name":"Tianjin University","ror":"https://ror.org/012tb2g32","country_code":"CN","type":"education","lineage":["https://openalex.org/I162868743"]},{"id":"https://openalex.org/I4210128676","display_name":"Human Computer Interaction (Switzerland)","ror":"https://ror.org/036dv6j71","country_code":"CH","type":"company","lineage":["https://openalex.org/I4210128676"]}],"countries":["CH","CN"],"is_corresponding":false,"raw_author_name":"Yutao Tian","raw_affiliation_strings":["Academy of Medical Engineering and Translational Medicine, Medical College","Haihe Laboratory of Brain-Computer Interaction and Human-Machine Integration","Tianjin Key Laboratory of Brain Science and Neuroengineering","Tianjin University"],"raw_orcid":"https://orcid.org/0000-0002-0622-5070","affiliations":[{"raw_affiliation_string":"Academy of Medical Engineering and Translational Medicine, Medical College","institution_ids":[]},{"raw_affiliation_string":"Haihe Laboratory of Brain-Computer Interaction and Human-Machine Integration","institution_ids":["https://openalex.org/I4210128676"]},{"raw_affiliation_string":"Tianjin Key Laboratory of Brain Science and Neuroengineering","institution_ids":[]},{"raw_affiliation_string":"Tianjin University","institution_ids":["https://openalex.org/I162868743"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.22044688,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"65","issue":"19","first_page":"10532","last_page":"10548"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T13052","display_name":"Molecular Communication and Nanonetworks","score":0.9926000237464905,"subfield":{"id":"https://openalex.org/subfields/2204","display_name":"Biomedical Engineering"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T13052","display_name":"Molecular Communication and Nanonetworks","score":0.9926000237464905,"subfield":{"id":"https://openalex.org/subfields/2204","display_name":"Biomedical Engineering"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10493","display_name":"Ion channel regulation and function","score":0.9860000014305115,"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/T11434","display_name":"Electrochemical Analysis and Applications","score":0.9803000092506409,"subfield":{"id":"https://openalex.org/subfields/1603","display_name":"Electrochemistry"},"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/allosteric-regulation","display_name":"Allosteric regulation","score":0.9430999755859375},{"id":"https://openalex.org/keywords/gating","display_name":"Gating","score":0.864799976348877},{"id":"https://openalex.org/keywords/sodium-channel","display_name":"Sodium channel","score":0.6654999852180481},{"id":"https://openalex.org/keywords/ligand","display_name":"Ligand (biochemistry)","score":0.5687999725341797},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.5511999726295471},{"id":"https://openalex.org/keywords/ion-channel","display_name":"Ion channel","score":0.5120999813079834},{"id":"https://openalex.org/keywords/extracellular","display_name":"Extracellular","score":0.4512999951839447},{"id":"https://openalex.org/keywords/conformational-change","display_name":"Conformational change","score":0.32659998536109924}],"concepts":[{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.9430999755859375},{"id":"https://openalex.org/C194544171","wikidata":"https://www.wikidata.org/wiki/Q21105679","display_name":"Gating","level":2,"score":0.864799976348877},{"id":"https://openalex.org/C50952357","wikidata":"https://www.wikidata.org/wiki/Q424960","display_name":"Sodium channel","level":3,"score":0.6654999852180481},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.5909000039100647},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.5687999725341797},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.5511999726295471},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5443000197410583},{"id":"https://openalex.org/C50254741","wikidata":"https://www.wikidata.org/wiki/Q62536","display_name":"Ion channel","level":3,"score":0.5120999813079834},{"id":"https://openalex.org/C28406088","wikidata":"https://www.wikidata.org/wiki/Q5571762","display_name":"Extracellular","level":2,"score":0.4512999951839447},{"id":"https://openalex.org/C2777339483","wikidata":"https://www.wikidata.org/wiki/Q647203","display_name":"Conformational change","level":2,"score":0.32659998536109924},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.32010000944137573},{"id":"https://openalex.org/C200170125","wikidata":"https://www.wikidata.org/wiki/Q969316","display_name":"Neurotransmission","level":3,"score":0.303600013256073},{"id":"https://openalex.org/C82617044","wikidata":"https://www.wikidata.org/wiki/Q418536","display_name":"Ligand-gated ion channel","level":4,"score":0.29089999198913574},{"id":"https://openalex.org/C32123652","wikidata":"https://www.wikidata.org/wiki/Q2451605","display_name":"Molecular switch","level":3,"score":0.28940001130104065},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.28929999470710754},{"id":"https://openalex.org/C79879829","wikidata":"https://www.wikidata.org/wiki/Q5571762","display_name":"Intracellular","level":2,"score":0.28839999437332153},{"id":"https://openalex.org/C145912823","wikidata":"https://www.wikidata.org/wiki/Q113558","display_name":"Dynamics (music)","level":2,"score":0.28360000252723694},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.2809000015258789},{"id":"https://openalex.org/C109964505","wikidata":"https://www.wikidata.org/wiki/Q3321436","display_name":"Allosteric enzyme","level":4,"score":0.2743000090122223},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.27079999446868896},{"id":"https://openalex.org/C127162648","wikidata":"https://www.wikidata.org/wiki/Q16858953","display_name":"Channel (broadcasting)","level":2,"score":0.26840001344680786},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.2669999897480011},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.26579999923706055},{"id":"https://openalex.org/C2775981520","wikidata":"https://www.wikidata.org/wiki/Q17156992","display_name":"Protein dynamics","level":3,"score":0.26460000872612},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.26159998774528503}],"mesh":[{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","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":"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":"D015640","descriptor_name":"Ion Channel Gating","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D015640","descriptor_name":"Ion Channel Gating","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D016571","descriptor_name":"Neural Networks, Computer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016571","descriptor_name":"Neural Networks, Computer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D019835","descriptor_name":"FMRFamide","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019835","descriptor_name":"FMRFamide","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019835","descriptor_name":"FMRFamide","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D019835","descriptor_name":"FMRFamide","qualifier_ui":"Q000494","qualifier_name":"pharmacology","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.5c01255","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c01255","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:41022701","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41022701","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":[],"awards":[{"id":"https://openalex.org/G1154159053","display_name":null,"funder_award_id":"32071103","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"},{"id":"https://openalex.org/G2400650423","display_name":null,"funder_award_id":"32471194","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"},{"id":"https://openalex.org/G8837670357","display_name":null,"funder_award_id":"2023YFF1204001","funder_id":"https://openalex.org/F4320335777","funder_display_name":"National Key Research and Development Program of China"}],"funders":[{"id":"https://openalex.org/F4320321001","display_name":"National Natural Science Foundation of China","ror":"https://ror.org/01h0zpd94"},{"id":"https://openalex.org/F4320335777","display_name":"National Key Research and Development Program of China","ror":null}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":56,"referenced_works":["https://openalex.org/W1529758720","https://openalex.org/W1565618263","https://openalex.org/W1820962178","https://openalex.org/W1965076207","https://openalex.org/W1967099353","https://openalex.org/W1974052375","https://openalex.org/W1974548955","https://openalex.org/W1976499671","https://openalex.org/W1990771438","https://openalex.org/W1995808589","https://openalex.org/W2008217058","https://openalex.org/W2013711061","https://openalex.org/W2029667189","https://openalex.org/W2034352765","https://openalex.org/W2043129540","https://openalex.org/W2043901383","https://openalex.org/W2044120209","https://openalex.org/W2053752711","https://openalex.org/W2067174909","https://openalex.org/W2070753604","https://openalex.org/W2104258075","https://openalex.org/W2106777560","https://openalex.org/W2122676372","https://openalex.org/W2128572087","https://openalex.org/W2132262459","https://openalex.org/W2150981663","https://openalex.org/W2164204379","https://openalex.org/W2170711116","https://openalex.org/W2206954826","https://openalex.org/W2227999806","https://openalex.org/W2265839167","https://openalex.org/W2317863386","https://openalex.org/W2513576822","https://openalex.org/W2555870966","https://openalex.org/W2733579469","https://openalex.org/W2767656747","https://openalex.org/W2784391196","https://openalex.org/W2789792412","https://openalex.org/W2893126194","https://openalex.org/W3004450557","https://openalex.org/W3030894768","https://openalex.org/W3046856725","https://openalex.org/W3048079539","https://openalex.org/W3177828909","https://openalex.org/W3186179742","https://openalex.org/W4220892969","https://openalex.org/W4281944609","https://openalex.org/W4309717866","https://openalex.org/W4313650892","https://openalex.org/W4379768709","https://openalex.org/W4385628925","https://openalex.org/W4390520644","https://openalex.org/W4391680694","https://openalex.org/W4405312877","https://openalex.org/W4406278116","https://openalex.org/W4409300698"],"related_works":[],"abstract_inverted_index":{"FMRFamide-activated":[0],"sodium":[1,15],"channels":[2,11],"(FaNaCs)":[3],"represent":[4],"a":[5,69,92,108,149,170,207,215],"unique":[6],"class":[7],"of":[8,61,78,129,153,161,211],"neuropeptide-gated":[9],"ion":[10],"within":[12],"the":[13,27,57,112,126,130,139,144,154,159,162,166,176,196,220,225],"degenerin/epithelial":[14],"channel":[16,37],"(DEG/ENaC)":[17],"superfamily.":[18],"While":[19],"cryo-electron":[20],"microscopy":[21],"has":[22],"revealed":[23,68],"static":[24],"binding":[25,194],"architectures,":[26],"dynamic":[28,93,209],"mechanisms":[29],"underlying":[30],"ligand":[31,98,114,193],"recognition,":[32],"allosteric":[33,189,201],"signal":[34],"transmission,":[35],"and":[36,82,100,136,169,199,223],"gating":[38,217],"remain":[39],"poorly":[40],"understood.":[41],"Here,":[42],"we":[43],"employed":[44],"microsecond-scale":[45],"molecular":[46],"dynamics":[47,77],"simulations":[48],"coupled":[49],"with":[50],"neural":[51,182],"relational":[52,183],"inference":[53,184],"analysis":[54,67],"to":[55,105,158,186],"elucidate":[56],"complete":[58],"activation":[59,72],"mechanism":[60,218],"FaNaC":[62,212],"at":[63],"atomic":[64],"resolution.":[65],"Our":[66],"sophisticated":[70],"multistage":[71],"process":[73],"initiated":[74],"by":[75],"coordinated":[76,150],"FaNaC-specific":[79],"insertions":[80],"SI1":[81,89],"SI2.":[83],"Spontaneous":[84],"FMRFamide-binding":[85],"events":[86],"suggested":[87],"that":[88,95,174,192],"functions":[90],"as":[91,107],"gate":[94],"facilitates":[96],"optimal":[97],"burial":[99],"stabilization,":[101],"while":[102],"SI2":[103],"appeared":[104],"serve":[106],"conformational":[109,122,172],"lid":[110],"stabilizing":[111],"bound":[113],"through":[115,143],"thermodynamically":[116],"favorable":[117],"induced-fit":[118],"mechanisms.":[119],"This":[120],"ligand-induced":[121],"change,":[123],"which":[124],"involves":[125],"cooperative":[127],"reorganization":[128,160],"three":[131],"peripheral":[132],"loops":[133],"(L1,":[134],"L2,":[135],"L3)":[137],"in":[138,165],"extracellular":[140,145,167],"domain,":[141,146,156],"propagates":[142],"particularly":[147],"via":[148],"rigid-body":[151],"motion":[152],"\u03b2-ball/palm":[155],"leading":[157],"central":[163],"\u03b2-sheet":[164],"vestibule":[168],"subsequent":[171],"wave":[173],"compacts":[175],"intracellular":[177],"vestibule.":[178],"We":[179],"further":[180],"leveraged":[181],"(NRI)":[185],"analyze":[187],"residue-level":[188],"networks,":[190],"demonstrating":[191],"enhances":[195],"network's":[197],"connectivity":[198],"reorganizes":[200],"communication":[202],"pathways.":[203],"These":[204],"findings":[205],"provide":[206],"high-resolution,":[208],"view":[210],"function,":[213],"revealing":[214],"novel":[216],"for":[219,227],"DEG/ENaC":[221],"superfamily":[222],"laying":[224],"foundation":[226],"future":[228],"studies":[229],"into":[230],"neuropeptide":[231],"modulation.":[232]},"counts_by_year":[],"updated_date":"2026-06-11T09:08:48.828518","created_date":"2025-10-10T00:00:00"}
