{"id":"https://openalex.org/W7154723248","doi":"https://doi.org/10.1021/acs.jcim.6c00945","title":"Untangling the Reaction Mechanism of the Polysaccharide Lyase PL42 Using QM/MM Metadynamics Simulations","display_name":"Untangling the Reaction Mechanism of the Polysaccharide Lyase PL42 Using QM/MM Metadynamics Simulations","publication_year":2026,"publication_date":"2026-04-17","ids":{"openalex":"https://openalex.org/W7154723248","doi":"https://doi.org/10.1021/acs.jcim.6c00945","pmid":"https://pubmed.ncbi.nlm.nih.gov/41996210"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.6c00945","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6c00945","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.6c00945","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5087592714","display_name":"Santiago Alonso\u2010Gil","orcid":"https://orcid.org/0000-0001-7596-8161"},"institutions":[{"id":"https://openalex.org/I202276237","display_name":"Medical University of Graz","ror":"https://ror.org/02n0bts35","country_code":"AT","type":"education","lineage":["https://openalex.org/I202276237"]},{"id":"https://openalex.org/I4210113448","display_name":"Institut Laue-Langevin","ror":"https://ror.org/01xtjs520","country_code":"FR","type":"facility","lineage":["https://openalex.org/I4210113448"]}],"countries":["AT","FR"],"is_corresponding":true,"raw_author_name":"Santiago Alonso-Gil","raw_affiliation_strings":["Institut Laue-Langevin","Laboratory of Computer-Aided Molecular Design, Division of Medicinal Chemistry, Otto-Loewi Research Center, Medical University of Graz, Neue Stiftintalstr. 6/III, GrazA-8010, Austria"],"raw_orcid":"https://orcid.org/0000-0001-7596-8161","affiliations":[{"raw_affiliation_string":"Institut Laue-Langevin","institution_ids":["https://openalex.org/I4210113448"]},{"raw_affiliation_string":"Laboratory of Computer-Aided Molecular Design, Division of Medicinal Chemistry, Otto-Loewi Research Center, Medical University of Graz, Neue Stiftintalstr. 6/III, GrazA-8010, Austria","institution_ids":["https://openalex.org/I202276237"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101402556","display_name":"Tatsuya Kondo","orcid":"https://orcid.org/0000-0002-7232-8238"},"institutions":[{"id":"https://openalex.org/I4387152983","display_name":"Osaka Metropolitan University","ror":"https://ror.org/01hvx5h04","country_code":"JP","type":"education","lineage":["https://openalex.org/I4387152983"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Tatsuya Kondo","raw_affiliation_strings":["Department of Applied Biological Chemistry, Graduate School of Agriculture","Osaka Metropolitan University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Applied Biological Chemistry, Graduate School of Agriculture","institution_ids":[]},{"raw_affiliation_string":"Osaka Metropolitan University","institution_ids":["https://openalex.org/I4387152983"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083281224","display_name":"Shinya Fushinobu","orcid":"https://orcid.org/0000-0003-1346-6435"},"institutions":[{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Shinya Fushinobu","raw_affiliation_strings":["Collaborative Research Institute for Innovative Microbiology","Department of Biotechnology","The University of Tokyo"],"raw_orcid":"https://orcid.org/0000-0003-1346-6435","affiliations":[{"raw_affiliation_string":"Collaborative Research Institute for Innovative Microbiology","institution_ids":[]},{"raw_affiliation_string":"Department of Biotechnology","institution_ids":[]},{"raw_affiliation_string":"The University of Tokyo","institution_ids":["https://openalex.org/I74801974"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5129913467","display_name":"Pedro A. S\u00e1nchez-Murcia","orcid":null},"institutions":[{"id":"https://openalex.org/I202276237","display_name":"Medical University of Graz","ror":"https://ror.org/02n0bts35","country_code":"AT","type":"education","lineage":["https://openalex.org/I202276237"]},{"id":"https://openalex.org/I4210117258","display_name":"BioTechMed-Graz","ror":"https://ror.org/02jfbm483","country_code":"AT","type":"facility","lineage":["https://openalex.org/I4210117258"]}],"countries":["AT"],"is_corresponding":true,"raw_author_name":"Pedro A. S\u00e1nchez-Murcia","raw_affiliation_strings":["BioTechMed-Graz, Mozartgasse 12/II, GrazA-8010, Austria","Laboratory of Computer-Aided Molecular Design, Division of Medicinal Chemistry, Otto-Loewi Research Center, Medical University of Graz, Neue Stiftintalstr. 6/III, GrazA-8010, Austria"],"raw_orcid":"https://orcid.org/0000-0001-8415-870X","affiliations":[{"raw_affiliation_string":"BioTechMed-Graz, Mozartgasse 12/II, GrazA-8010, Austria","institution_ids":["https://openalex.org/I4210117258"]},{"raw_affiliation_string":"Laboratory of Computer-Aided Molecular Design, Division of Medicinal Chemistry, Otto-Loewi Research Center, Medical University of Graz, Neue Stiftintalstr. 6/III, GrazA-8010, Austria","institution_ids":["https://openalex.org/I202276237"]}]}],"institutions":[],"countries_distinct_count":3,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5087592714","https://openalex.org/A5129913467"],"corresponding_institution_ids":["https://openalex.org/I202276237","https://openalex.org/I4210113448","https://openalex.org/I4210117258"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.71133049,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"66","issue":"9","first_page":"5463","last_page":"5470"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12192","display_name":"Polysaccharides Composition and Applications","score":0.39100000262260437,"subfield":{"id":"https://openalex.org/subfields/1106","display_name":"Food Science"},"field":{"id":"https://openalex.org/fields/11","display_name":"Agricultural and Biological Sciences"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12192","display_name":"Polysaccharides Composition and Applications","score":0.39100000262260437,"subfield":{"id":"https://openalex.org/subfields/1106","display_name":"Food Science"},"field":{"id":"https://openalex.org/fields/11","display_name":"Agricultural and Biological Sciences"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10869","display_name":"Polysaccharides and Plant Cell Walls","score":0.29910001158714294,"subfield":{"id":"https://openalex.org/subfields/1110","display_name":"Plant Science"},"field":{"id":"https://openalex.org/fields/11","display_name":"Agricultural and Biological Sciences"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10835","display_name":"Carbohydrate Chemistry and Synthesis","score":0.05640000104904175,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic 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/metadynamics","display_name":"Metadynamics","score":0.8758000135421753},{"id":"https://openalex.org/keywords/reaction-mechanism","display_name":"Reaction mechanism","score":0.5217000246047974},{"id":"https://openalex.org/keywords/polysaccharide","display_name":"Polysaccharide","score":0.4542999863624573},{"id":"https://openalex.org/keywords/lyase","display_name":"Lyase","score":0.40959998965263367},{"id":"https://openalex.org/keywords/mechanism","display_name":"Mechanism (biology)","score":0.40720000863075256},{"id":"https://openalex.org/keywords/reaction-intermediate","display_name":"Reaction intermediate","score":0.32199999690055847}],"concepts":[{"id":"https://openalex.org/C62752575","wikidata":"https://www.wikidata.org/wiki/Q6822487","display_name":"Metadynamics","level":3,"score":0.8758000135421753},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7472000122070312},{"id":"https://openalex.org/C65024703","wikidata":"https://www.wikidata.org/wiki/Q373406","display_name":"Reaction mechanism","level":3,"score":0.5217000246047974},{"id":"https://openalex.org/C100817775","wikidata":"https://www.wikidata.org/wiki/Q134219","display_name":"Polysaccharide","level":2,"score":0.4542999863624573},{"id":"https://openalex.org/C2777269803","wikidata":"https://www.wikidata.org/wiki/Q407727","display_name":"Lyase","level":3,"score":0.40959998965263367},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.40720000863075256},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.37059998512268066},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.3425000011920929},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.3402999937534332},{"id":"https://openalex.org/C105768512","wikidata":"https://www.wikidata.org/wiki/Q7458208","display_name":"Reaction intermediate","level":3,"score":0.32199999690055847},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.29919999837875366},{"id":"https://openalex.org/C148898269","wikidata":"https://www.wikidata.org/wiki/Q1108792","display_name":"Kinetics","level":2,"score":0.2971000075340271},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.2896000146865845},{"id":"https://openalex.org/C2778977261","wikidata":"https://www.wikidata.org/wiki/Q11358","display_name":"Carbohydrate","level":2,"score":0.27900001406669617},{"id":"https://openalex.org/C18762648","wikidata":"https://www.wikidata.org/wiki/Q42213","display_name":"Work (physics)","level":2,"score":0.27810001373291016},{"id":"https://openalex.org/C2994592520","wikidata":"https://www.wikidata.org/wiki/Q5090496","display_name":"Substrate specificity","level":3,"score":0.2669999897480011},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.25290000438690186}],"mesh":[{"descriptor_ui":"D011133","descriptor_name":"Polysaccharide-Lyases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011133","descriptor_name":"Polysaccharide-Lyases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011133","descriptor_name":"Polysaccharide-Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D011133","descriptor_name":"Polysaccharide-Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"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":"D011789","descriptor_name":"Quantum Theory","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011789","descriptor_name":"Quantum Theory","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","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":"D055162","descriptor_name":"Biocatalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055162","descriptor_name":"Biocatalysis","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":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.6c00945","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6c00945","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:41996210","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41996210","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:13169297","is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13169297/","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":"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.6c00945","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6c00945","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/G2184838017","display_name":null,"funder_award_id":"24H02269","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G4218351080","display_name":null,"funder_award_id":"23H00322","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G8578109376","display_name":null,"funder_award_id":"72479","funder_id":"https://openalex.org/F4320328086","funder_display_name":"Bundesministerium f\u00fcr Bildung, Wissenschaft und Forschung"}],"funders":[{"id":"https://openalex.org/F4320326239","display_name":"Medizinische Universit\u00e4t Graz","ror":"https://ror.org/02n0bts35"},{"id":"https://openalex.org/F4320328086","display_name":"Bundesministerium f\u00fcr Bildung, Wissenschaft und Forschung","ror":"https://ror.org/03gng8t46"},{"id":"https://openalex.org/F4320334764","display_name":"Japan Society for the Promotion of Science","ror":"https://ror.org/00hhkn466"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":37,"referenced_works":["https://openalex.org/W1981368803","https://openalex.org/W1982414593","https://openalex.org/W1988091937","https://openalex.org/W1993177346","https://openalex.org/W2004303971","https://openalex.org/W2028372777","https://openalex.org/W2054704030","https://openalex.org/W2057806291","https://openalex.org/W2060079863","https://openalex.org/W2092157292","https://openalex.org/W2112154906","https://openalex.org/W2146411229","https://openalex.org/W2149655632","https://openalex.org/W2155417823","https://openalex.org/W2970740744","https://openalex.org/W2989052455","https://openalex.org/W3023475125","https://openalex.org/W3033695897","https://openalex.org/W3046033601","https://openalex.org/W3157649705","https://openalex.org/W3183493659","https://openalex.org/W3216134202","https://openalex.org/W4206602797","https://openalex.org/W4213434824","https://openalex.org/W4308548012","https://openalex.org/W4387060248","https://openalex.org/W4391930674","https://openalex.org/W4400451272","https://openalex.org/W4405370192","https://openalex.org/W4407771512","https://openalex.org/W4408568833","https://openalex.org/W4411683580","https://openalex.org/W4415615086","https://openalex.org/W4416191266","https://openalex.org/W4416896044","https://openalex.org/W7125675387","https://openalex.org/W7131425247"],"related_works":[],"abstract_inverted_index":{"Polysaccharide":[0],"lyase":[1,47,163],"family":[2],"42":[3],"(PL42)":[4],"enzymes":[5],"cleave":[6],"terminal":[7],"Rha-GlcA":[8],"motifs":[9],"from":[10,72,148],"gum":[11],"arabic":[12],"through":[13,121,165],"\u03b2-elimination.":[14],"However,":[15],"the":[16,41,45,50,67,80,94,106,131,135,157],"neutron-based":[17],"catalytic":[18,68,145],"proposal":[19],"for":[20],"FoRham1":[21,48],"has":[22],"not":[23],"been":[24],"validated":[25],"on":[26],"a":[27,56,98,143],"free-energy":[28],"surface.":[29],"Here,":[30],"we":[31],"combine":[32],"QM/MM":[33],"well-tempered":[34],"metadynamics":[35,110],"with":[36,70,126],"umbrella":[37,122],"sampling":[38],"to":[39,117],"analyze":[40],"reaction":[42],"mechanism":[43],"of":[44,150],"PL42":[46,139],"at":[49],"atomic":[51],"level.":[52],"The":[53,84,109],"calculations":[54],"support":[55],"concerted":[57],"yet":[58],"highly":[59],"asynchronous":[60],"syn":[61],"\u03b2-elimination,":[62],"where":[63],"His85":[64],"functions":[65],"as":[66],"base/acid,":[69],"assistance":[71],"Asp83":[73],"and":[74,93,152],"doubly":[75],"protonated":[76],"His105.":[77],"Arg166":[78],"stabilizes":[79],"glucuronate":[81],"carboxylate":[82],"electrostatically.":[83],"reactive":[85],"substrate":[86],"conformation":[87],"is":[88,115],"an":[89],"inverse-chair":[90],"1C4":[91,99,101],"state,":[92],"+1":[95],"sugar":[96],"follows":[97],"\u2192":[100,102],"1H2":[103],"pathway":[104],"along":[105],"minimum-free-energy":[107],"route.":[108],"barrier":[111],"(\u223c19":[112],"kcal":[113,119],"mol\u20131)":[114],"refined":[116],"17.7":[118],"mol\u20131":[120],"sampling,":[123],"aligning":[124],"reasonably":[125],"experimental":[127,133],"data.":[128],"Beyond":[129],"confirming":[130],"proposed":[132],"mechanism,":[134],"results":[136],"demonstrate":[137],"that":[138],"catalyzes":[140],"\u03b2-elimination":[141],"via":[142],"histidine-based":[144],"system":[146],"distinct":[147],"those":[149],"PL7":[151],"PL38.":[153],"Additionally,":[154],"they":[155],"expand":[156],"emerging":[158],"conformational":[159],"framework":[160],"linking":[161],"polysaccharide":[162],"mechanisms":[164],"their":[166],"product-ring":[167],"geometries.":[168]},"counts_by_year":[],"updated_date":"2026-05-17T08:19:37.847499","created_date":"2026-04-18T00:00:00"}