{"id":"https://openalex.org/W4406429353","doi":"https://doi.org/10.1021/acs.jcim.4c01860","title":"MEDOC: A Fast, Scalable, and Mathematically Exact Algorithm for the Site-Specific Prediction of the Protonation Degree in Large Disordered Proteins","display_name":"MEDOC: A Fast, Scalable, and Mathematically Exact Algorithm for the Site-Specific Prediction of the Protonation Degree in Large Disordered Proteins","publication_year":2025,"publication_date":"2025-01-16","ids":{"openalex":"https://openalex.org/W4406429353","doi":"https://doi.org/10.1021/acs.jcim.4c01860","pmid":"https://pubmed.ncbi.nlm.nih.gov/39817437"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.4c01860","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.4c01860","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","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":"hybrid","oa_url":"https://doi.org/10.1021/acs.jcim.4c01860","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5058456848","display_name":"Martin J. Fossat","orcid":"https://orcid.org/0000-0003-3078-2886"},"institutions":[{"id":"https://openalex.org/I4210164321","display_name":"Max Planck Institute of Immunobiology and Epigenetics","ror":"https://ror.org/058xzat49","country_code":"DE","type":"facility","lineage":["https://openalex.org/I149899117","https://openalex.org/I4210164321"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Martin J. Fossat","raw_affiliation_strings":["Max-Planck-Institut f\u00fcr Immunbiologie und Epigenetik (MPI-IE), St\u00fcbeweg 51, 79108 Freiburg im Breisgau, Germany"],"affiliations":[{"raw_affiliation_string":"Max-Planck-Institut f\u00fcr Immunbiologie und Epigenetik (MPI-IE), St\u00fcbeweg 51, 79108 Freiburg im Breisgau, Germany","institution_ids":["https://openalex.org/I4210164321"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5058456848"],"corresponding_institution_ids":["https://openalex.org/I4210164321"],"apc_list":null,"apc_paid":null,"fwci":0.5406,"has_fulltext":true,"cited_by_count":1,"citation_normalized_percentile":{"value":0.58253185,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":91,"max":95},"biblio":{"volume":"65","issue":"2","first_page":"873","last_page":"881"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11162","display_name":"Enzyme Structure and Function","score":0.9997000098228455,"subfield":{"id":"https://openalex.org/subfields/2505","display_name":"Materials Chemistry"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11162","display_name":"Enzyme Structure and Function","score":0.9997000098228455,"subfield":{"id":"https://openalex.org/subfields/2505","display_name":"Materials Chemistry"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9995999932289124,"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":0.9925000071525574,"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/degree","display_name":"Degree (music)","score":0.7353004217147827},{"id":"https://openalex.org/keywords/algorithm","display_name":"Algorithm","score":0.5241813063621521},{"id":"https://openalex.org/keywords/protonation","display_name":"Protonation","score":0.5224080085754395},{"id":"https://openalex.org/keywords/scalability","display_name":"Scalability","score":0.5181437730789185},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.48318353295326233},{"id":"https://openalex.org/keywords/statistical-physics","display_name":"Statistical physics","score":0.35898661613464355},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.35534924268722534},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.2198689877986908}],"concepts":[{"id":"https://openalex.org/C2775997480","wikidata":"https://www.wikidata.org/wiki/Q586277","display_name":"Degree (music)","level":2,"score":0.7353004217147827},{"id":"https://openalex.org/C11413529","wikidata":"https://www.wikidata.org/wiki/Q8366","display_name":"Algorithm","level":1,"score":0.5241813063621521},{"id":"https://openalex.org/C30095370","wikidata":"https://www.wikidata.org/wiki/Q899488","display_name":"Protonation","level":3,"score":0.5224080085754395},{"id":"https://openalex.org/C48044578","wikidata":"https://www.wikidata.org/wiki/Q727490","display_name":"Scalability","level":2,"score":0.5181437730789185},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.48318353295326233},{"id":"https://openalex.org/C121864883","wikidata":"https://www.wikidata.org/wiki/Q677916","display_name":"Statistical physics","level":1,"score":0.35898661613464355},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.35534924268722534},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.2198689877986908},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0},{"id":"https://openalex.org/C77088390","wikidata":"https://www.wikidata.org/wiki/Q8513","display_name":"Database","level":1,"score":0.0},{"id":"https://openalex.org/C145148216","wikidata":"https://www.wikidata.org/wiki/Q36496","display_name":"Ion","level":2,"score":0.0},{"id":"https://openalex.org/C24890656","wikidata":"https://www.wikidata.org/wiki/Q82811","display_name":"Acoustics","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D006863","descriptor_name":"Hydrogen-Ion Concentration","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006863","descriptor_name":"Hydrogen-Ion Concentration","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":"D008958","descriptor_name":"Models, Molecular","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":"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":"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":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D011522","descriptor_name":"Protons","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011522","descriptor_name":"Protons","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011522","descriptor_name":"Protons","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011522","descriptor_name":"Protons","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011522","descriptor_name":"Protons","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D064267","descriptor_name":"Intrinsically Disordered Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D064267","descriptor_name":"Intrinsically Disordered Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D064267","descriptor_name":"Intrinsically Disordered Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D064267","descriptor_name":"Intrinsically Disordered Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D064267","descriptor_name":"Intrinsically Disordered Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.4c01860","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.4c01860","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:39817437","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/39817437","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:11776046","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11776046","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11776046/pdf/ci4c01860.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1021/acs.jcim.4c01860","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.4c01860","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[{"id":"https://openalex.org/G8096683007","display_name":null,"funder_award_id":"FA9550-20-1-0241","funder_id":"https://openalex.org/F4320338279","funder_display_name":"Air Force Office of Scientific Research"},{"id":"https://openalex.org/G8765840595","display_name":null,"funder_award_id":"R01NS121114","funder_id":"https://openalex.org/F4320337359","funder_display_name":"National Institute of Neurological Disorders and Stroke"}],"funders":[{"id":"https://openalex.org/F4320322434","display_name":"Max-Planck-Gesellschaft","ror":"https://ror.org/01hhn8329"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337359","display_name":"National Institute of Neurological Disorders and Stroke","ror":"https://ror.org/01s5ya894"},{"id":"https://openalex.org/F4320338279","display_name":"Air Force Office of Scientific Research","ror":"https://ror.org/011e9bt93"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":51,"referenced_works":["https://openalex.org/W1489827117","https://openalex.org/W1574461844","https://openalex.org/W1578694919","https://openalex.org/W1895367194","https://openalex.org/W1968733906","https://openalex.org/W1968751925","https://openalex.org/W1970022221","https://openalex.org/W2005064054","https://openalex.org/W2007735374","https://openalex.org/W2010868958","https://openalex.org/W2022383019","https://openalex.org/W2024762727","https://openalex.org/W2030173443","https://openalex.org/W2049670194","https://openalex.org/W2062241319","https://openalex.org/W2063206968","https://openalex.org/W2070962887","https://openalex.org/W2076742999","https://openalex.org/W2092147666","https://openalex.org/W2113912523","https://openalex.org/W2141775785","https://openalex.org/W2144252381","https://openalex.org/W2233253752","https://openalex.org/W2314823775","https://openalex.org/W2468070683","https://openalex.org/W2594406263","https://openalex.org/W2764210034","https://openalex.org/W2783855936","https://openalex.org/W2794054829","https://openalex.org/W2888614490","https://openalex.org/W2916884115","https://openalex.org/W2938874044","https://openalex.org/W2966687748","https://openalex.org/W3020734054","https://openalex.org/W3080821559","https://openalex.org/W3103110929","https://openalex.org/W3105581675","https://openalex.org/W3119734745","https://openalex.org/W3129011282","https://openalex.org/W3157808708","https://openalex.org/W3214870576","https://openalex.org/W3215954549","https://openalex.org/W3216570014","https://openalex.org/W4205794662","https://openalex.org/W4220734384","https://openalex.org/W4220811910","https://openalex.org/W4224278557","https://openalex.org/W4254466969","https://openalex.org/W4285589483","https://openalex.org/W4313490807","https://openalex.org/W4392915605"],"related_works":["https://openalex.org/W945805037","https://openalex.org/W2021989727","https://openalex.org/W2081371352","https://openalex.org/W2070272790","https://openalex.org/W2021444944","https://openalex.org/W1993510903","https://openalex.org/W2950239819","https://openalex.org/W1571167194","https://openalex.org/W2125084167","https://openalex.org/W1978802871"],"abstract_inverted_index":{"Intrinsically":[0],"disordered":[1,66],"regions":[2],"are":[3,10],"found":[4],"in":[5,88,242,260],"most":[6,107],"eukaryotic":[7],"proteins":[8,108,208],"and":[9,14,171,253],"enriched":[11],"with":[12,51,184,256],"positively":[13],"negatively":[15],"charged":[16],"residues.":[17],"While":[18],"it":[19],"is":[20,61],"often":[21],"convenient":[22],"to":[23,125,156,187,220],"assume":[24],"that":[25,37,74,146],"these":[26],"residues":[27,87],"follow":[28],"their":[29],"model-compound":[30],"p<i>K</i><sub>a</sub>":[31,49,231,247,258],"values,":[32],"recent":[33],"work":[34],"has":[35],"shown":[36],"local":[38,137],"charge":[39,59,72,104,166,204],"effects":[40],"(charge":[41],"regulation)":[42],"can":[43,75,148],"upshift":[44],"or":[45],"downshift":[46],"side":[47],"chain":[48],"values":[50,232,248,259],"major":[52],"consequences":[53],"for":[54,207,249],"molecular":[55],"function.":[56],"Despite":[57],"this,":[58],"regulation":[60,80],"rarely":[62],"considered":[63],"when":[64],"investigating":[65],"regions.":[67],"The":[68],"number":[69,84,152,202,212],"of":[70,81,85,101,106,119,129,131,140,153,164,179,193,200,203,213,227,230,245],"potential":[71],"microstates":[73,205],"be":[76],"populated":[77],"through":[78],"acid/base":[79],"a":[82,89,132,210,224],"given":[83],"ionizable":[86,142,214],"sequence,":[90],"<i>N</i>,":[91],"scales":[92],"as":[93],"\u223c2<sup><i>N</i></sup>.":[94],"This":[95],"exponential":[96],"scaling":[97],"makes":[98],"the":[99,102,127,136,151,158,165,177,180,190,197,201,228,234,243],"assessment":[100],"full":[103],"landscape":[105,167],"computationally":[109],"intractable.":[110],"To":[111],"address":[112],"this":[113],"problem,":[114],"we":[115,147],"developed":[116],"\"multisite":[117],"extent":[118],"deprotonation":[120],"originating":[121],"from":[122],"context\"":[123],"(MEDOC)":[124],"determine":[126,157],"degree":[128],"protonation":[130],"protein":[133],"based":[134],"on":[135],"sequence":[138],"context":[139],"each":[141],"residue.":[143],"We":[144,217],"show":[145,240],"drastically":[149],"reduce":[150],"parameters":[154],"necessary":[155],"full,":[159],"analytical":[160],"Boltzmann":[161],"partition":[162],"function":[163],"at":[168],"both":[169],"global":[170,225],"site-specific":[172],"levels.":[173],"Our":[174,238],"algorithm":[175],"applies":[176],"structure":[178],"<i>q</i>-canonical":[181],"ensemble,":[182],"combined":[183],"novel":[185],"strategies":[186],"rapidly":[188],"obtain":[189],"minimal":[191],"set":[192],"parameters,":[194],"thereby":[195],"circumventing":[196],"combinatorial":[198],"explosion":[199],"even":[206],"containing":[209],"large":[211],"amino":[215,251],"acids.":[216],"apply":[218],"MEDOC":[219],"several":[221],"sequences,":[222],"including":[223],"analysis":[226],"distribution":[229,244],"across":[233],"entire":[235],"DisProt":[236],"database.":[237],"results":[239],"differences":[241],"predicted":[246],"different":[250],"acids":[252],"good":[254],"agreement":[255],"NMR-measured":[257],"proteins.":[261]},"counts_by_year":[{"year":2025,"cited_by_count":1}],"updated_date":"2026-03-20T23:20:44.827607","created_date":"2025-10-10T00:00:00"}
