{"id":"https://openalex.org/W4414853388","doi":"https://doi.org/10.1021/acs.jcim.5c01152","title":"Combining Reactive Quantum-Mechanical Molecular-Dynamics Simulations with Mutagenesis, Crystallography, and Enzyme Kinetics to Reveal Plausible Steps of Isocyanide Hydratase Catalysis","display_name":"Combining Reactive Quantum-Mechanical Molecular-Dynamics Simulations with Mutagenesis, Crystallography, and Enzyme Kinetics to Reveal Plausible Steps of Isocyanide Hydratase Catalysis","publication_year":2025,"publication_date":"2025-10-06","ids":{"openalex":"https://openalex.org/W4414853388","doi":"https://doi.org/10.1021/acs.jcim.5c01152","pmid":"https://pubmed.ncbi.nlm.nih.gov/41051317"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c01152","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c01152","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-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","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.5c01152","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5078920954","display_name":"Rae Corrigan","orcid":"https://orcid.org/0000-0003-3628-9347"},"institutions":[{"id":"https://openalex.org/I1343871089","display_name":"Los Alamos National Laboratory","ror":"https://ror.org/01e41cf67","country_code":"US","type":"facility","lineage":["https://openalex.org/I1330989302","https://openalex.org/I1343871089","https://openalex.org/I198811213","https://openalex.org/I4210120050"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rae A. Corrigan Grove","raw_affiliation_strings":["Los Alamos National Laboratory","Theoretical Division","Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States"],"raw_orcid":"https://orcid.org/0000-0003-3628-9347","affiliations":[{"raw_affiliation_string":"Los Alamos National Laboratory","institution_ids":["https://openalex.org/I1343871089"]},{"raw_affiliation_string":"Theoretical Division","institution_ids":[]},{"raw_affiliation_string":"Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States","institution_ids":["https://openalex.org/I1343871089"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005735997","display_name":"Michael A. Moxley","orcid":"https://orcid.org/0000-0002-6988-1964"},"institutions":[{"id":"https://openalex.org/I36486460","display_name":"University of Nebraska at Kearney","ror":"https://ror.org/04d5mb615","country_code":"US","type":"education","lineage":["https://openalex.org/I36486460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael A. Moxley","raw_affiliation_strings":["Department of Chemistry","University of Nebraska-Kearney","Department of Chemistry, University of Nebraska-Kearney, Kearney, Nebraska 68849, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry","institution_ids":[]},{"raw_affiliation_string":"University of Nebraska-Kearney","institution_ids":["https://openalex.org/I36486460"]},{"raw_affiliation_string":"Department of Chemistry, University of Nebraska-Kearney, Kearney, Nebraska 68849, United States","institution_ids":["https://openalex.org/I36486460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082049238","display_name":"Christian F. A. Negre","orcid":"https://orcid.org/0000-0001-5720-0255"},"institutions":[{"id":"https://openalex.org/I1343871089","display_name":"Los Alamos National Laboratory","ror":"https://ror.org/01e41cf67","country_code":"US","type":"facility","lineage":["https://openalex.org/I1330989302","https://openalex.org/I1343871089","https://openalex.org/I198811213","https://openalex.org/I4210120050"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Christian F. A. Negre","raw_affiliation_strings":["Los Alamos National Laboratory","Theoretical Division","Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Los Alamos National Laboratory","institution_ids":["https://openalex.org/I1343871089"]},{"raw_affiliation_string":"Theoretical Division","institution_ids":[]},{"raw_affiliation_string":"Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States","institution_ids":["https://openalex.org/I1343871089"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059713249","display_name":"M. J. Cawkwell","orcid":"https://orcid.org/0000-0002-8919-3368"},"institutions":[{"id":"https://openalex.org/I1343871089","display_name":"Los Alamos National Laboratory","ror":"https://ror.org/01e41cf67","country_code":"US","type":"facility","lineage":["https://openalex.org/I1330989302","https://openalex.org/I1343871089","https://openalex.org/I198811213","https://openalex.org/I4210120050"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Marc J. Cawkwell","raw_affiliation_strings":["Los Alamos National Laboratory","Theoretical Division","Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States"],"raw_orcid":"https://orcid.org/0000-0002-8919-3368","affiliations":[{"raw_affiliation_string":"Los Alamos National Laboratory","institution_ids":["https://openalex.org/I1343871089"]},{"raw_affiliation_string":"Theoretical Division","institution_ids":[]},{"raw_affiliation_string":"Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States","institution_ids":["https://openalex.org/I1343871089"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081056746","display_name":"Anders M. N. Niklasson","orcid":"https://orcid.org/0000-0003-1856-4982"},"institutions":[{"id":"https://openalex.org/I1343871089","display_name":"Los Alamos National Laboratory","ror":"https://ror.org/01e41cf67","country_code":"US","type":"facility","lineage":["https://openalex.org/I1330989302","https://openalex.org/I1343871089","https://openalex.org/I198811213","https://openalex.org/I4210120050"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Anders M. N. Niklasson","raw_affiliation_strings":["Los Alamos National Laboratory","Theoretical Division","Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Los Alamos National Laboratory","institution_ids":["https://openalex.org/I1343871089"]},{"raw_affiliation_string":"Theoretical Division","institution_ids":[]},{"raw_affiliation_string":"Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States","institution_ids":["https://openalex.org/I1343871089"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025653234","display_name":"Susan M. Mniszewski","orcid":"https://orcid.org/0000-0002-0077-0537"},"institutions":[{"id":"https://openalex.org/I1343871089","display_name":"Los Alamos National Laboratory","ror":"https://ror.org/01e41cf67","country_code":"US","type":"facility","lineage":["https://openalex.org/I1330989302","https://openalex.org/I1343871089","https://openalex.org/I198811213","https://openalex.org/I4210120050"]},{"id":"https://openalex.org/I4210164862","display_name":"Artificial Intelligence in Medicine (Canada)","ror":"https://ror.org/05p590m36","country_code":"CA","type":"company","lineage":["https://openalex.org/I4210164862"]}],"countries":["CA","US"],"is_corresponding":false,"raw_author_name":"Susan M. Mniszewski","raw_affiliation_strings":["Computing and Artificial Intelligence Division","Los Alamos National Laboratory","Computing and Artificial Intelligence Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States"],"raw_orcid":"https://orcid.org/0000-0002-0077-0537","affiliations":[{"raw_affiliation_string":"Computing and Artificial Intelligence Division","institution_ids":["https://openalex.org/I4210164862"]},{"raw_affiliation_string":"Los Alamos National Laboratory","institution_ids":["https://openalex.org/I1343871089"]},{"raw_affiliation_string":"Computing and Artificial Intelligence Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States","institution_ids":["https://openalex.org/I1343871089"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Nathan Smith","orcid":null},"institutions":[{"id":"https://openalex.org/I114395901","display_name":"University of Nebraska\u2013Lincoln","ror":"https://ror.org/043mer456","country_code":"US","type":"education","lineage":["https://openalex.org/I114395901"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nathan Smith","raw_affiliation_strings":["Department of Biochemistry","University of Nebraska-Lincoln","Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry","institution_ids":[]},{"raw_affiliation_string":"University of Nebraska-Lincoln","institution_ids":["https://openalex.org/I114395901"]},{"raw_affiliation_string":"Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States","institution_ids":["https://openalex.org/I114395901"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5116323318","display_name":"Kevin Prososki","orcid":null},"institutions":[{"id":"https://openalex.org/I114395901","display_name":"University of Nebraska\u2013Lincoln","ror":"https://ror.org/043mer456","country_code":"US","type":"education","lineage":["https://openalex.org/I114395901"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kevin Prososki","raw_affiliation_strings":["Department of Biochemistry","University of Nebraska-Lincoln","Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry","institution_ids":[]},{"raw_affiliation_string":"University of Nebraska-Lincoln","institution_ids":["https://openalex.org/I114395901"]},{"raw_affiliation_string":"Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States","institution_ids":["https://openalex.org/I114395901"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5041973369","display_name":"Mark A. Wilson","orcid":"https://orcid.org/0000-0001-6317-900X"},"institutions":[{"id":"https://openalex.org/I114395901","display_name":"University of Nebraska\u2013Lincoln","ror":"https://ror.org/043mer456","country_code":"US","type":"education","lineage":["https://openalex.org/I114395901"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Mark A. Wilson","raw_affiliation_strings":["Department of Biochemistry","University of Nebraska-Lincoln","Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States"],"raw_orcid":"https://orcid.org/0000-0001-6317-900X","affiliations":[{"raw_affiliation_string":"Department of Biochemistry","institution_ids":[]},{"raw_affiliation_string":"University of Nebraska-Lincoln","institution_ids":["https://openalex.org/I114395901"]},{"raw_affiliation_string":"Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States","institution_ids":["https://openalex.org/I114395901"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5114374642","display_name":"Michael E. Wall","orcid":"https://orcid.org/0000-0003-1000-688X"},"institutions":[{"id":"https://openalex.org/I1343871089","display_name":"Los Alamos National Laboratory","ror":"https://ror.org/01e41cf67","country_code":"US","type":"facility","lineage":["https://openalex.org/I1330989302","https://openalex.org/I1343871089","https://openalex.org/I198811213","https://openalex.org/I4210120050"]},{"id":"https://openalex.org/I4210164862","display_name":"Artificial Intelligence in Medicine (Canada)","ror":"https://ror.org/05p590m36","country_code":"CA","type":"company","lineage":["https://openalex.org/I4210164862"]}],"countries":["CA","US"],"is_corresponding":true,"raw_author_name":"Michael E. Wall","raw_affiliation_strings":["Computing and Artificial Intelligence Division","Los Alamos National Laboratory","Computing and Artificial Intelligence Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States"],"raw_orcid":"https://orcid.org/0000-0003-1000-688X","affiliations":[{"raw_affiliation_string":"Computing and Artificial Intelligence Division","institution_ids":["https://openalex.org/I4210164862"]},{"raw_affiliation_string":"Los Alamos National Laboratory","institution_ids":["https://openalex.org/I1343871089"]},{"raw_affiliation_string":"Computing and Artificial Intelligence Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States","institution_ids":["https://openalex.org/I1343871089"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5041973369","https://openalex.org/A5114374642"],"corresponding_institution_ids":["https://openalex.org/I114395901","https://openalex.org/I1343871089","https://openalex.org/I4210164862"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.16524236,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"65","issue":"20","first_page":"11079","last_page":"11093"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"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"}},"topics":[{"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/T11162","display_name":"Enzyme Structure and Function","score":0.9991999864578247,"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/T12827","display_name":"Biochemical and Molecular Research","score":0.9939000010490417,"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/kinetics","display_name":"Kinetics","score":0.6904000043869019},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.6416000127792358},{"id":"https://openalex.org/keywords/protonation","display_name":"Protonation","score":0.6147000193595886},{"id":"https://openalex.org/keywords/isocyanide","display_name":"Isocyanide","score":0.47769999504089355},{"id":"https://openalex.org/keywords/enzyme-kinetics","display_name":"Enzyme kinetics","score":0.45019999146461487},{"id":"https://openalex.org/keywords/enzyme","display_name":"Enzyme","score":0.4293000102043152},{"id":"https://openalex.org/keywords/enzyme-catalysis","display_name":"Enzyme catalysis","score":0.4074999988079071}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7936999797821045},{"id":"https://openalex.org/C148898269","wikidata":"https://www.wikidata.org/wiki/Q1108792","display_name":"Kinetics","level":2,"score":0.6904000043869019},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.6416000127792358},{"id":"https://openalex.org/C30095370","wikidata":"https://www.wikidata.org/wiki/Q899488","display_name":"Protonation","level":3,"score":0.6147000193595886},{"id":"https://openalex.org/C2777010268","wikidata":"https://www.wikidata.org/wiki/Q421897","display_name":"Isocyanide","level":2,"score":0.47769999504089355},{"id":"https://openalex.org/C56856141","wikidata":"https://www.wikidata.org/wiki/Q883112","display_name":"Enzyme kinetics","level":4,"score":0.45019999146461487},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.4293000102043152},{"id":"https://openalex.org/C69118441","wikidata":"https://www.wikidata.org/wiki/Q2941663","display_name":"Enzyme catalysis","level":3,"score":0.4074999988079071},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.4032000005245209},{"id":"https://openalex.org/C36663273","wikidata":"https://www.wikidata.org/wiki/Q209082","display_name":"Chemical kinetics","level":3,"score":0.3587999939918518},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.3467999994754791},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.335099995136261},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.3091999888420105},{"id":"https://openalex.org/C105768512","wikidata":"https://www.wikidata.org/wiki/Q7458208","display_name":"Reaction intermediate","level":3,"score":0.3073999881744385},{"id":"https://openalex.org/C63338738","wikidata":"https://www.wikidata.org/wiki/Q287862","display_name":"Catalytic cycle","level":3,"score":0.2815999984741211},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.2680000066757202},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.26739999651908875},{"id":"https://openalex.org/C192937433","wikidata":"https://www.wikidata.org/wiki/Q2134627","display_name":"Reactive intermediate","level":3,"score":0.26600000262260437},{"id":"https://openalex.org/C65024703","wikidata":"https://www.wikidata.org/wiki/Q373406","display_name":"Reaction mechanism","level":3,"score":0.2581999897956848}],"mesh":[{"descriptor_ui":"D003486","descriptor_name":"Cyanides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D003486","descriptor_name":"Cyanides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D003486","descriptor_name":"Cyanides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D003486","descriptor_name":"Cyanides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D006836","descriptor_name":"Hydro-Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"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":"D007700","descriptor_name":"Kinetics","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":"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":"D016296","descriptor_name":"Mutagenesis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016296","descriptor_name":"Mutagenesis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016296","descriptor_name":"Mutagenesis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016296","descriptor_name":"Mutagenesis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D018360","descriptor_name":"Crystallography, X-Ray","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018360","descriptor_name":"Crystallography, X-Ray","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018360","descriptor_name":"Crystallography, X-Ray","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018360","descriptor_name":"Crystallography, X-Ray","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020134","descriptor_name":"Catalytic Domain","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020134","descriptor_name":"Catalytic Domain","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020134","descriptor_name":"Catalytic Domain","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020134","descriptor_name":"Catalytic Domain","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":true},{"descriptor_ui":"D055162","descriptor_name":"Biocatalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D055162","descriptor_name":"Biocatalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D055162","descriptor_name":"Biocatalysis","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},{"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.5c01152","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c01152","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-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:41051317","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41051317","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:europepmc.org:11376089","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12570138","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1021/acs.jcim.5c01152","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c01152","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-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","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/G2716827339","display_name":null,"funder_award_id":"R15 GM152925","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G2856537951","display_name":null,"funder_award_id":"P30GM133894","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G3714894102","display_name":null,"funder_award_id":"5P20GM103427","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G4029151897","display_name":null,"funder_award_id":"P20 GM103427","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G4042998212","display_name":null,"funder_award_id":"LANLE8AN","funder_id":"https://openalex.org/F4320337480","funder_display_name":"Basic Energy Sciences"},{"id":"https://openalex.org/G429856259","display_name":null,"funder_award_id":"R35 GM153337","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G8479889628","display_name":null,"funder_award_id":"1R15GM152925-01","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"}],"funders":[{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"},{"id":"https://openalex.org/F4320337480","display_name":"Basic Energy Sciences","ror":"https://ror.org/05mg91w61"},{"id":"https://openalex.org/F4320338304","display_name":"Los Alamos National Laboratory","ror":"https://ror.org/01e41cf67"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":116,"referenced_works":["https://openalex.org/W1531395020","https://openalex.org/W1645422644","https://openalex.org/W1650728208","https://openalex.org/W1967882612","https://openalex.org/W1971773700","https://openalex.org/W1973899958","https://openalex.org/W1975276775","https://openalex.org/W1976106600","https://openalex.org/W1978629909","https://openalex.org/W1981021420","https://openalex.org/W1991282644","https://openalex.org/W1992601434","https://openalex.org/W1994105222","https://openalex.org/W1994578519","https://openalex.org/W1998885514","https://openalex.org/W1999602967","https://openalex.org/W2001462701","https://openalex.org/W2007876421","https://openalex.org/W2008216430","https://openalex.org/W2008735595","https://openalex.org/W2022696619","https://openalex.org/W2028046413","https://openalex.org/W2029667189","https://openalex.org/W2030976617","https://openalex.org/W2031597111","https://openalex.org/W2035832119","https://openalex.org/W2045239955","https://openalex.org/W2048350769","https://openalex.org/W2048946954","https://openalex.org/W2054103452","https://openalex.org/W2057333774","https://openalex.org/W2062320396","https://openalex.org/W2066451762","https://openalex.org/W2066531623","https://openalex.org/W2073841855","https://openalex.org/W2079346455","https://openalex.org/W2085894510","https://openalex.org/W2087138441","https://openalex.org/W2087784840","https://openalex.org/W2088380112","https://openalex.org/W2090063868","https://openalex.org/W2093221728","https://openalex.org/W2094259887","https://openalex.org/W2094516606","https://openalex.org/W2104489082","https://openalex.org/W2105614327","https://openalex.org/W2110808180","https://openalex.org/W2141704677","https://openalex.org/W2144081223","https://openalex.org/W2151752974","https://openalex.org/W2153693853","https://openalex.org/W2155358697","https://openalex.org/W2163341755","https://openalex.org/W2165385023","https://openalex.org/W2171893485","https://openalex.org/W2286402374","https://openalex.org/W2288670848","https://openalex.org/W2317841013","https://openalex.org/W2319101143","https://openalex.org/W2322378280","https://openalex.org/W2322864600","https://openalex.org/W2331727781","https://openalex.org/W2504749891","https://openalex.org/W2563055040","https://openalex.org/W2592558869","https://openalex.org/W2593502667","https://openalex.org/W2612571999","https://openalex.org/W2619609791","https://openalex.org/W2735366672","https://openalex.org/W2765322245","https://openalex.org/W2770709523","https://openalex.org/W2805692389","https://openalex.org/W2887092515","https://openalex.org/W2902628125","https://openalex.org/W2907925938","https://openalex.org/W2911198211","https://openalex.org/W2973087556","https://openalex.org/W2973457155","https://openalex.org/W2990504690","https://openalex.org/W3010690049","https://openalex.org/W3033761676","https://openalex.org/W3080330343","https://openalex.org/W3100638071","https://openalex.org/W3106403548","https://openalex.org/W3136988020","https://openalex.org/W3139891715","https://openalex.org/W3163144368","https://openalex.org/W3181318326","https://openalex.org/W3185317322","https://openalex.org/W3192979275","https://openalex.org/W3213289343","https://openalex.org/W3217528490","https://openalex.org/W4205805942","https://openalex.org/W4214944872","https://openalex.org/W4225113041","https://openalex.org/W4226057859","https://openalex.org/W4230546834","https://openalex.org/W4243725249","https://openalex.org/W4248872320","https://openalex.org/W4283373028","https://openalex.org/W4285724617","https://openalex.org/W4289839737","https://openalex.org/W4310117699","https://openalex.org/W4310438948","https://openalex.org/W4318586121","https://openalex.org/W4366178422","https://openalex.org/W4367040931","https://openalex.org/W4378952892","https://openalex.org/W4382344685","https://openalex.org/W4382501724","https://openalex.org/W4386055296","https://openalex.org/W4386526707","https://openalex.org/W4389166036","https://openalex.org/W4393246017","https://openalex.org/W4393864411","https://openalex.org/W4410776365"],"related_works":[],"abstract_inverted_index":{"A":[0],"complete":[1],"understanding":[2],"of":[3,9,21,57,76,86,99,112,124,138,148,177,203,229,247,261],"enzyme":[4,174,235,253],"mechanisms":[5,85,254],"requires":[6],"atomistic":[7],"details":[8],"chemical":[10],"reactions.":[11],"Quantum-based":[12],"molecular":[13,41,97],"dynamics":[14,42,118],"simulations":[15,75],"(QMD)":[16],"are":[17,188,221],"a":[18,47,63,109,120,135,141,195],"potential":[19],"source":[20],"this":[22],"information,":[23],"but":[24],"trade-offs":[25],"between":[26],"accuracy":[27,51],"and":[28,80,116,133,172,179,186,266],"computational":[29],"cost":[30,56],"have":[31],"limited":[32],"their":[33],"use.":[34],"We":[35],"previously":[36],"developed":[37],"extended":[38],"Lagrangian":[39],"Born-Oppenheimer":[40],"(XL-BOMD)":[43],"methods":[44],"that":[45,197,249],"leverage":[46],"negligible":[48],"compromise":[49],"in":[50,89,144,194,208,216,233],"to":[52,83,130,165,190,223,239],"substantially":[53],"decrease":[54],"the":[55,68,125,145,154,158,184,191,201,204,209,227,245,259],"QMD":[58,65,95,160,264],"simulations.":[59,210],"Here,":[60],"we":[61,168],"develop":[62],"reactive":[64,78,159,263],"approach":[66,161,265],"using":[67,157],"latest":[69],"XL-BOMD":[70],"formulation,":[71],"which":[72],"enables":[73],"efficient":[74],"highly":[77],"systems,":[79],"use":[81],"it":[82],"investigate":[84],"intermediate":[87],"formation":[88,132],"isocyanide":[90,126],"hydratase":[91],"(ICH)":[92],"catalysis.":[93,150],"In":[94],"simulations,":[96],"analogs":[98],"ICH":[100,149,166],"active":[101],"site":[102],"residues":[103],"reacted":[104],"with":[105,200],"para-nitrophenyl":[106],"isocyanide,":[107],"forming":[108],"thioimidate.":[110],"Analysis":[111],"simulated":[113],"atomic":[114],"configurational":[115],"charge":[117],"revealed":[119],"pathway":[121,155],"where":[122],"protonation":[123],"carbon":[127],"occurs":[128],"prior":[129],"thioimidate":[131],"suggested":[134],"possible":[136],"role":[137],"Asp17":[139],"as":[140],"proton":[142],"donor":[143],"early":[146],"phase":[147],"To":[151],"test":[152],"whether":[153],"seen":[156,207],"might":[162],"be":[163],"relevant":[164],"catalysis,":[167],"performed":[169],"X-ray":[170],"crystallography":[171],"pre-steady-state":[173],"kinetics":[175,187],"studies":[176],"wild-type":[178],"D17N":[180,192],"mutant":[181],"ICH.":[182],"Both":[183],"structure":[185],"sensitive":[189],"mutation":[193],"manner":[196],"is":[198],"consistent":[199],"order":[202],"reaction":[205],"steps":[206,231],"Mobile":[211],"protons":[212,257],"play":[213],"essential":[214],"roles":[215],"many":[217,234],"enzymes,":[218],"yet":[219],"they":[220],"difficult":[222],"observe":[224],"experimentally,":[225],"making":[226],"ordering":[228],"proton-dependent":[230],"ambiguous":[232],"mechanisms.":[236],"The":[237],"ability":[238],"directly":[240],"simulate":[241],"model":[242],"reactions":[243],"for":[244],"design":[246],"experiments":[248],"provide":[250],"information":[251],"about":[252],"involving":[255],"mobile":[256],"demonstrates":[258],"significance":[260],"our":[262],"motivates":[267],"further":[268],"biological":[269],"applications.":[270]},"counts_by_year":[],"updated_date":"2026-08-01T09:00:35.917206","created_date":"2025-10-10T00:00:00"}
