{"id":"https://openalex.org/W2293632061","doi":"https://doi.org/10.1371/journal.pcbi.1004811","title":"Dynamic Modelling Reveals \u2018Hotspots\u2019 on the Pathway to Enzyme-Substrate Complex Formation","display_name":"Dynamic Modelling Reveals \u2018Hotspots\u2019 on the Pathway to Enzyme-Substrate Complex Formation","publication_year":2016,"publication_date":"2016-03-11","ids":{"openalex":"https://openalex.org/W2293632061","doi":"https://doi.org/10.1371/journal.pcbi.1004811","mag":"2293632061","pmid":"https://pubmed.ncbi.nlm.nih.gov/26967332"},"language":"en","primary_location":{"id":"doi:10.1371/journal.pcbi.1004811","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1004811","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004811&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","datacite","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004811&type=printable","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5069017475","display_name":"Shane E. Gordon","orcid":"https://orcid.org/0000-0003-3964-8317"},"institutions":[{"id":"https://openalex.org/I196829312","display_name":"La Trobe University","ror":"https://ror.org/01rxfrp27","country_code":"AU","type":"education","lineage":["https://openalex.org/I196829312"]},{"id":"https://openalex.org/I4210120068","display_name":"IBM Research - Australia","ror":"https://ror.org/027r3nx49","country_code":"AU","type":"facility","lineage":["https://openalex.org/I1341412227","https://openalex.org/I4210114115","https://openalex.org/I4210120068"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"Shane E. Gordon","raw_affiliation_strings":["Computational Biophysics, IBM Research - Australia, Carlton, Victoria, Australia","Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia"],"affiliations":[{"raw_affiliation_string":"Computational Biophysics, IBM Research - Australia, Carlton, Victoria, Australia","institution_ids":["https://openalex.org/I4210120068"]},{"raw_affiliation_string":"Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia","institution_ids":["https://openalex.org/I196829312"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050276384","display_name":"Daniel K. Weber","orcid":"https://orcid.org/0000-0001-8400-767X"},"institutions":[{"id":"https://openalex.org/I4210120068","display_name":"IBM Research - Australia","ror":"https://ror.org/027r3nx49","country_code":"AU","type":"facility","lineage":["https://openalex.org/I1341412227","https://openalex.org/I4210114115","https://openalex.org/I4210120068"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"Daniel K. Weber","raw_affiliation_strings":["Computational Biophysics, IBM Research - Australia, Carlton, Victoria, Australia"],"affiliations":[{"raw_affiliation_string":"Computational Biophysics, IBM Research - Australia, Carlton, Victoria, Australia","institution_ids":["https://openalex.org/I4210120068"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010775868","display_name":"Matthew T. Downton","orcid":"https://orcid.org/0000-0002-4693-1965"},"institutions":[{"id":"https://openalex.org/I4210120068","display_name":"IBM Research - Australia","ror":"https://ror.org/027r3nx49","country_code":"AU","type":"facility","lineage":["https://openalex.org/I1341412227","https://openalex.org/I4210114115","https://openalex.org/I4210120068"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"Matthew T. Downton","raw_affiliation_strings":["Computational Biophysics, IBM Research - Australia, Carlton, Victoria, Australia"],"affiliations":[{"raw_affiliation_string":"Computational Biophysics, IBM Research - Australia, Carlton, Victoria, Australia","institution_ids":["https://openalex.org/I4210120068"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5106447615","display_name":"John Wagner","orcid":null},"institutions":[{"id":"https://openalex.org/I4210120068","display_name":"IBM Research - Australia","ror":"https://ror.org/027r3nx49","country_code":"AU","type":"facility","lineage":["https://openalex.org/I1341412227","https://openalex.org/I4210114115","https://openalex.org/I4210120068"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"John Wagner","raw_affiliation_strings":["Computational Biophysics, IBM Research - Australia, Carlton, Victoria, Australia"],"affiliations":[{"raw_affiliation_string":"Computational Biophysics, IBM Research - Australia, Carlton, Victoria, Australia","institution_ids":["https://openalex.org/I4210120068"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5089976475","display_name":"Matthew A. Perugini","orcid":"https://orcid.org/0000-0001-8052-5584"},"institutions":[{"id":"https://openalex.org/I196829312","display_name":"La Trobe University","ror":"https://ror.org/01rxfrp27","country_code":"AU","type":"education","lineage":["https://openalex.org/I196829312"]}],"countries":["AU"],"is_corresponding":true,"raw_author_name":"Matthew A. Perugini","raw_affiliation_strings":["Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia"],"affiliations":[{"raw_affiliation_string":"Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia","institution_ids":["https://openalex.org/I196829312"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5089976475"],"corresponding_institution_ids":["https://openalex.org/I196829312"],"apc_list":{"value":2655,"currency":"USD","value_usd":2655},"apc_paid":{"value":2655,"currency":"USD","value_usd":2655},"fwci":0.9549,"has_fulltext":true,"cited_by_count":13,"citation_normalized_percentile":{"value":0.73387097,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":97},"biblio":{"volume":"12","issue":"3","first_page":"e1004811","last_page":"e1004811"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11162","display_name":"Enzyme Structure and Function","score":0.9998999834060669,"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":0.9998999834060669,"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":0.9987999796867371,"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/active-site","display_name":"Active site","score":0.6007816195487976},{"id":"https://openalex.org/keywords/binding-site","display_name":"Binding site","score":0.4950844347476959},{"id":"https://openalex.org/keywords/lyase","display_name":"Lyase","score":0.49431777000427246},{"id":"https://openalex.org/keywords/allosteric-regulation","display_name":"Allosteric regulation","score":0.48685282468795776},{"id":"https://openalex.org/keywords/protein-structure","display_name":"Protein structure","score":0.4624249339103699},{"id":"https://openalex.org/keywords/plasma-protein-binding","display_name":"Plasma protein binding","score":0.45554250478744507},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.43609946966171265},{"id":"https://openalex.org/keywords/enzyme","display_name":"Enzyme","score":0.4129948019981384},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.39768439531326294},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.37847191095352173},{"id":"https://openalex.org/keywords/stereochemistry","display_name":"Stereochemistry","score":0.33690351247787476}],"concepts":[{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.6007816195487976},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.4950844347476959},{"id":"https://openalex.org/C2777269803","wikidata":"https://www.wikidata.org/wiki/Q407727","display_name":"Lyase","level":3,"score":0.49431777000427246},{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.48685282468795776},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.4624249339103699},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.45554250478744507},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.43609946966171265},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.4129948019981384},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.39768439531326294},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.37847191095352173},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.33690351247787476}],"mesh":[{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002384","descriptor_name":"Catalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002384","descriptor_name":"Catalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002384","descriptor_name":"Catalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004789","descriptor_name":"Enzyme Activation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004789","descriptor_name":"Enzyme Activation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004789","descriptor_name":"Enzyme Activation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004795","descriptor_name":"Enzyme Stability","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004795","descriptor_name":"Enzyme Stability","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004795","descriptor_name":"Enzyme Stability","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","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":"D013210","descriptor_name":"Staphylococcus","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D013210","descriptor_name":"Staphylococcus","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D013210","descriptor_name":"Staphylococcus","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D013379","descriptor_name":"Substrate Specificity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013379","descriptor_name":"Substrate Specificity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013379","descriptor_name":"Substrate Specificity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019289","descriptor_name":"Pyruvic Acid","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D019289","descriptor_name":"Pyruvic Acid","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D019289","descriptor_name":"Pyruvic Acid","qualifier_ui":"Q000737","qualifier_name":"chemistry","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},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":10,"locations":[{"id":"doi:10.1371/journal.pcbi.1004811","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1004811","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004811&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},{"id":"pmid:26967332","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/26967332","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":"PLoS computational biology","raw_type":null},{"id":"pmh:oai:jupiter.its.unimelb.edu.au:11343/258411","is_oa":true,"landing_page_url":"http://hdl.handle.net/11343/258411","pdf_url":"http://hdl.handle.net/11343/258411","source":{"id":"https://openalex.org/S4377196259","display_name":"Minerva Access (University of Melbourne)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I165779595","host_organization_name":"The University of Melbourne","host_organization_lineage":["https://openalex.org/I165779595"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Journal Article"},{"id":"pmh:doi:10.26181/22028729","is_oa":true,"landing_page_url":null,"pdf_url":null,"source":{"id":"https://openalex.org/S4406922384","display_name":"Open MIND","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"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":null,"raw_type":"Journal contribution"},{"id":"pmh:oai:RePEc:plo:pcbi00:1004811","is_oa":false,"landing_page_url":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004811","pdf_url":null,"source":{"id":"https://openalex.org/S4306401271","display_name":"RePEc: Research Papers in Economics","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I77793887","host_organization_name":"Federal Reserve Bank of St. Louis","host_organization_lineage":["https://openalex.org/I77793887"],"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"},{"id":"pmh:oai:doaj.org/article:1864205eb32849c9aa5042de8ab32e85","is_oa":true,"landing_page_url":"https://doaj.org/article/1864205eb32849c9aa5042de8ab32e85","pdf_url":null,"source":{"id":"https://openalex.org/S112646816","display_name":"SHILAP Revista de lepidopterolog\u00eda","issn_l":"0300-5267","issn":["0300-5267","2340-4078"],"is_oa":true,"is_in_doaj":true,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PLoS Computational Biology, Vol 12, Iss 3, p e1004811 (2016)","raw_type":"article"},{"id":"pmh:oai:figshare.com:article/22028729","is_oa":true,"landing_page_url":"https://figshare.com/articles/journal_contribution/Dynamic_Modelling_Reveals_Hotspots_on_the_Pathway_to_Enzyme-Substrate_Complex_Formation/22028729","pdf_url":null,"source":{"id":"https://openalex.org/S4377196282","display_name":"Figshare","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I4210132348","host_organization_name":"Figshare (United Kingdom)","host_organization_lineage":["https://openalex.org/I4210132348"],"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":"","raw_type":"Text"},{"id":"pmh:oai:figshare.com:article/3966489","is_oa":true,"landing_page_url":"https://figshare.com/articles/dataset/Dynamic_Modelling_Reveals_Hotspots_on_the_Pathway_to_Enzyme-Substrate_Complex_Formation/3966489","pdf_url":null,"source":{"id":"https://openalex.org/S4377196282","display_name":"Figshare","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I4210132348","host_organization_name":"Figshare (United Kingdom)","host_organization_lineage":["https://openalex.org/I4210132348"],"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":"","raw_type":"Dataset"},{"id":"pmh:oai:pubmedcentral.nih.gov:4788353","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4788353","pdf_url":null,"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":"PLoS Comput Biol","raw_type":"Text"},{"id":"doi:10.26181/22028729.v1","is_oa":true,"landing_page_url":"https://doi.org/10.26181/22028729.v1","pdf_url":null,"source":{"id":"https://openalex.org/S7407052018","display_name":"La Trobe University","issn_l":null,"issn":[],"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":null,"raw_source_name":null,"raw_type":"article-journal"}],"best_oa_location":{"id":"doi:10.1371/journal.pcbi.1004811","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1004811","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004811&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.4300000071525574,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"awards":[],"funders":[{"id":"https://openalex.org/F4320320974","display_name":"University of Melbourne","ror":"https://ror.org/01ej9dk98"},{"id":"https://openalex.org/F4320322858","display_name":"State Government of Victoria","ror":"https://ror.org/02xvc5r05"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2293632061.pdf","grobid_xml":"https://content.openalex.org/works/W2293632061.grobid-xml"},"referenced_works_count":57,"referenced_works":["https://openalex.org/W1505087925","https://openalex.org/W1512749823","https://openalex.org/W1976499671","https://openalex.org/W1977150791","https://openalex.org/W1990814944","https://openalex.org/W1995348059","https://openalex.org/W1997237169","https://openalex.org/W2000777346","https://openalex.org/W2001904989","https://openalex.org/W2003949305","https://openalex.org/W2004381102","https://openalex.org/W2005839192","https://openalex.org/W2008407101","https://openalex.org/W2011370119","https://openalex.org/W2013787134","https://openalex.org/W2014445318","https://openalex.org/W2016889234","https://openalex.org/W2017634849","https://openalex.org/W2017896410","https://openalex.org/W2024223411","https://openalex.org/W2027219026","https://openalex.org/W2027408247","https://openalex.org/W2028046413","https://openalex.org/W2029564559","https://openalex.org/W2029667189","https://openalex.org/W2033763457","https://openalex.org/W2035250994","https://openalex.org/W2035687084","https://openalex.org/W2041791898","https://openalex.org/W2043020420","https://openalex.org/W2050333027","https://openalex.org/W2055484248","https://openalex.org/W2065652080","https://openalex.org/W2066327917","https://openalex.org/W2066961392","https://openalex.org/W2070359441","https://openalex.org/W2075243501","https://openalex.org/W2077947928","https://openalex.org/W2079280525","https://openalex.org/W2081479643","https://openalex.org/W2081645999","https://openalex.org/W2085769836","https://openalex.org/W2105617347","https://openalex.org/W2106140689","https://openalex.org/W2111339528","https://openalex.org/W2127322768","https://openalex.org/W2133620840","https://openalex.org/W2143869273","https://openalex.org/W2144272172","https://openalex.org/W2146538795","https://openalex.org/W2150981663","https://openalex.org/W2164997719","https://openalex.org/W2403554753","https://openalex.org/W2506969691","https://openalex.org/W2786774014","https://openalex.org/W2905250049","https://openalex.org/W3101066868"],"related_works":["https://openalex.org/W1988180979","https://openalex.org/W1992459676","https://openalex.org/W2063082974","https://openalex.org/W2937705502","https://openalex.org/W2069536318","https://openalex.org/W2009511126","https://openalex.org/W2043020420","https://openalex.org/W2792325116","https://openalex.org/W1979420505","https://openalex.org/W1964840468"],"abstract_inverted_index":{"Dihydrodipicolinate":[0],"synthase":[1],"(DHDPS)":[2],"catalyzes":[3],"the":[4,9,27,73,78,91,100,118,123,139,171,196,201,223,229],"first":[5],"committed":[6],"step":[7],"in":[8,35,53,116,141,206,218,237],"diaminopimelate":[10],"pathway":[11],"of":[12,26,62,99,120,152,170,181,231],"bacteria,":[13,30],"yielding":[14],"amino":[15],"acids":[16],"required":[17],"for":[18,138,228],"cell":[19],"wall":[20],"and":[21,67,83,157,200],"protein":[22],"biosyntheses.":[23],"The":[24,104],"essentiality":[25],"enzyme":[28],"to":[29,71,111,164,225],"coupled":[31],"with":[32,130,194],"its":[33,84],"absence":[34],"humans,":[36],"validates":[37],"DHDPS":[38,56,76,142,159,234],"as":[39],"an":[40,135,214],"antibacterial":[41],"drug":[42,45],"target.":[43],"Conventional":[44],"design":[46],"efforts":[47],"have":[48,112],"thus":[49],"far":[50],"been":[51],"unsuccessful":[52],"identifying":[54],"potent":[55],"inhibitors.":[57],"Here,":[58],"we":[59,184],"make":[60],"use":[61],"contemporary":[63],"molecular":[64],"dynamics":[65],"simulation":[66],"Markov":[68],"state":[69],"models":[70],"explore":[72],"interactions":[74],"between":[75,155],"from":[77,126],"human":[79],"pathogen":[80],"Staphylococcus":[81],"aureus":[82],"cognate":[85],"substrate,":[86],"pyruvate.":[87],"Our":[88,209],"simulations":[89],"recover":[90],"crystallographic":[92],"DHDPS-pyruvate":[93],"complex":[94],"without":[95],"a":[96,113,166,238],"priori":[97],"knowledge":[98],"final":[101],"bound":[102],"structure.":[103],"highly":[105,167],"conserved":[106,168],"residue":[107,140,160],"Arg140":[108,161],"was":[109,162],"found":[110,163],"pivotal":[114],"role":[115,137],"coordinating":[117],"entry":[119],"pyruvate":[121,156],"into":[122,213],"active":[124],"site":[125],"bulk":[127],"solvent,":[128],"consistent":[129,193],"previous":[131],"kinetic":[132],"reports,":[133],"indicating":[134],"indirect":[136],"catalysis.":[143],"A":[144],"metastable":[145],"binding":[146,172,177,188,203],"intermediate":[147],"characterized":[148],"by":[149],"multiple":[150],"points":[151],"intermolecular":[153],"interaction":[154,217],"key":[158],"be":[165,226],"feature":[169],"trajectory":[173],"when":[174],"comparing":[175],"alternative":[176],"pathways.":[178],"By":[179],"means":[180],"umbrella":[182],"sampling":[183],"show":[185],"that":[186,221],"these":[187],"intermediates":[189],"are":[190],"thermodynamically":[191],"metastable,":[192],"both":[195],"available":[197],"experimental":[198],"data":[199],"substrate":[202],"model":[204],"presented":[205],"this":[207],"study.":[208],"results":[210],"provide":[211],"insight":[212],"important":[215],"enzyme-substrate":[216],"atomistic":[219],"detail":[220],"offers":[222],"potential":[224],"exploited":[227],"discovery":[230],"more":[232],"effective":[233],"inhibitors":[235],"and,":[236],"broader":[239],"sense,":[240],"dynamic":[241],"protein-drug":[242],"interactions.":[243]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":3},{"year":2023,"cited_by_count":1},{"year":2021,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2018,"cited_by_count":3},{"year":2017,"cited_by_count":3}],"updated_date":"2026-04-04T16:13:02.066488","created_date":"2025-10-10T00:00:00"}
