{"id":"https://openalex.org/W2043205949","doi":"https://doi.org/10.1371/journal.pcbi.1004207","title":"Thermal Stabilization of Dihydrofolate Reductase Using Monte Carlo Unfolding Simulations and Its Functional Consequences","display_name":"Thermal Stabilization of Dihydrofolate Reductase Using Monte Carlo Unfolding Simulations and Its Functional Consequences","publication_year":2015,"publication_date":"2015-04-23","ids":{"openalex":"https://openalex.org/W2043205949","doi":"https://doi.org/10.1371/journal.pcbi.1004207","mag":"2043205949","pmid":"https://pubmed.ncbi.nlm.nih.gov/25905910"},"language":"en","primary_location":{"id":"doi:10.1371/journal.pcbi.1004207","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1004207","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004207&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","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004207&type=printable","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5011692902","display_name":"Jian Tian","orcid":"https://orcid.org/0000-0002-9997-6518"},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210138501","display_name":"Chinese Academy of Agricultural Sciences","ror":"https://ror.org/0313jb750","country_code":"CN","type":"government","lineage":["https://openalex.org/I4210127390","https://openalex.org/I4210138501","https://openalex.org/I4210151987"]},{"id":"https://openalex.org/I4210144193","display_name":"Biotechnology Research Institute","ror":"https://ror.org/04eba5983","country_code":"CA","type":"facility","lineage":["https://openalex.org/I4210144193","https://openalex.org/I4210159778"]},{"id":"https://openalex.org/I4210167153","display_name":"Biotechnology Research Institute","ror":"https://ror.org/05vm76w92","country_code":"CN","type":"facility","lineage":["https://openalex.org/I4210127390","https://openalex.org/I4210138501","https://openalex.org/I4210151987","https://openalex.org/I4210167153"]}],"countries":["CA","CN","US"],"is_corresponding":true,"raw_author_name":"Jian Tian","raw_affiliation_strings":["Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China","Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America","Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China","institution_ids":["https://openalex.org/I4210144193"]},{"raw_affiliation_string":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America","institution_ids":["https://openalex.org/I136199984"]},{"raw_affiliation_string":"Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China","institution_ids":["https://openalex.org/I4210138501","https://openalex.org/I4210167153"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039093196","display_name":"Jaie Woodard","orcid":"https://orcid.org/0000-0001-5505-7803"},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jaie C. Woodard","raw_affiliation_strings":["Graduate Program in Biophysics, Harvard University, Cambridge, Massachusetts, United States of America"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate Program in Biophysics, Harvard University, Cambridge, Massachusetts, United States of America","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5105435144","display_name":"Andrew Whitney","orcid":null},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Andrew Whitney","raw_affiliation_strings":["Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5082765817","display_name":"Eugene I. Shakhnovich","orcid":"https://orcid.org/0000-0002-4769-2265"},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Eugene I. Shakhnovich","raw_affiliation_strings":["Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America","institution_ids":["https://openalex.org/I136199984"]}]}],"institutions":[],"countries_distinct_count":3,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5011692902","https://openalex.org/A5039093196","https://openalex.org/A5082765817","https://openalex.org/A5105435144"],"corresponding_institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210138501","https://openalex.org/I4210144193","https://openalex.org/I4210167153"],"apc_list":{"value":2655,"currency":"USD","value_usd":2655},"apc_paid":{"value":2655,"currency":"USD","value_usd":2655},"fwci":2.3417,"has_fulltext":true,"cited_by_count":43,"citation_normalized_percentile":{"value":0.88782376,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":99},"biblio":{"volume":"11","issue":"4","first_page":"e1004207","last_page":"e1004207"},"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":0.9990000128746033,"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/T11124","display_name":"Protein purification and stability","score":0.9934999942779541,"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/dihydrofolate-reductase","display_name":"Dihydrofolate reductase","score":0.857890784740448},{"id":"https://openalex.org/keywords/monte-carlo-method","display_name":"Monte Carlo method","score":0.5864342451095581},{"id":"https://openalex.org/keywords/mutant","display_name":"Mutant","score":0.5075138807296753},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.4725964665412903},{"id":"https://openalex.org/keywords/thermodynamics","display_name":"Thermodynamics","score":0.45309191942214966},{"id":"https://openalex.org/keywords/denaturation","display_name":"Denaturation (fissile materials)","score":0.45042288303375244},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.43423402309417725},{"id":"https://openalex.org/keywords/active-site","display_name":"Active site","score":0.43186309933662415},{"id":"https://openalex.org/keywords/equilibrium-unfolding","display_name":"Equilibrium unfolding","score":0.42080923914909363},{"id":"https://openalex.org/keywords/protein-folding","display_name":"Protein folding","score":0.3418944478034973},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.24569904804229736},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.21335268020629883},{"id":"https://openalex.org/keywords/enzyme","display_name":"Enzyme","score":0.19748148322105408},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.18389761447906494},{"id":"https://openalex.org/keywords/mathematics","display_name":"Mathematics","score":0.0749993622303009}],"concepts":[{"id":"https://openalex.org/C2781320022","wikidata":"https://www.wikidata.org/wiki/Q417149","display_name":"Dihydrofolate reductase","level":3,"score":0.857890784740448},{"id":"https://openalex.org/C19499675","wikidata":"https://www.wikidata.org/wiki/Q232207","display_name":"Monte Carlo method","level":2,"score":0.5864342451095581},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.5075138807296753},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4725964665412903},{"id":"https://openalex.org/C97355855","wikidata":"https://www.wikidata.org/wiki/Q11473","display_name":"Thermodynamics","level":1,"score":0.45309191942214966},{"id":"https://openalex.org/C2776923230","wikidata":"https://www.wikidata.org/wiki/Q16955798","display_name":"Denaturation (fissile materials)","level":2,"score":0.45042288303375244},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.43423402309417725},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.43186309933662415},{"id":"https://openalex.org/C175188612","wikidata":"https://www.wikidata.org/wiki/Q5384491","display_name":"Equilibrium unfolding","level":3,"score":0.42080923914909363},{"id":"https://openalex.org/C204328495","wikidata":"https://www.wikidata.org/wiki/Q847556","display_name":"Protein folding","level":2,"score":0.3418944478034973},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.24569904804229736},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.21335268020629883},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.19748148322105408},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.18389761447906494},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.0749993622303009},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0},{"id":"https://openalex.org/C13965031","wikidata":"https://www.wikidata.org/wiki/Q243545","display_name":"Nuclear chemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","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":"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":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D009010","descriptor_name":"Monte Carlo Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009010","descriptor_name":"Monte Carlo Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009010","descriptor_name":"Monte Carlo Method","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":"D011489","descriptor_name":"Protein Denaturation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011489","descriptor_name":"Protein Denaturation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011489","descriptor_name":"Protein Denaturation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013762","descriptor_name":"Tetrahydrofolate Dehydrogenase","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D013762","descriptor_name":"Tetrahydrofolate Dehydrogenase","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D013762","descriptor_name":"Tetrahydrofolate Dehydrogenase","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D013762","descriptor_name":"Tetrahydrofolate Dehydrogenase","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D013762","descriptor_name":"Tetrahydrofolate Dehydrogenase","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D013762","descriptor_name":"Tetrahydrofolate Dehydrogenase","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D013762","descriptor_name":"Tetrahydrofolate Dehydrogenase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D013762","descriptor_name":"Tetrahydrofolate Dehydrogenase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D013762","descriptor_name":"Tetrahydrofolate Dehydrogenase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D015233","descriptor_name":"Models, Statistical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015233","descriptor_name":"Models, Statistical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015233","descriptor_name":"Models, Statistical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016297","descriptor_name":"Mutagenesis, Site-Directed","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016297","descriptor_name":"Mutagenesis, Site-Directed","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016297","descriptor_name":"Mutagenesis, Site-Directed","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017510","descriptor_name":"Protein Folding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017510","descriptor_name":"Protein Folding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017510","descriptor_name":"Protein Folding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D044366","descriptor_name":"Transition Temperature","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D044366","descriptor_name":"Transition Temperature","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D044366","descriptor_name":"Transition Temperature","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":7,"locations":[{"id":"doi:10.1371/journal.pcbi.1004207","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1004207","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004207&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:25905910","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/25905910","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:dash.harvard.edu:1/16120836","is_oa":true,"landing_page_url":"http://nrs.harvard.edu/urn-3:HUL.InstRepos:16120836","pdf_url":null,"source":{"id":"https://openalex.org/S4306401540","display_name":"Digital Access to Scholarship at Harvard (DASH) (Harvard University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I136199984","host_organization_name":"Harvard University","host_organization_lineage":["https://openalex.org/I136199984"],"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":"Journal Article"},{"id":"pmh:oai:RePEc:plo:pcbi00:1004207","is_oa":false,"landing_page_url":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004207","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:0de565c5f8ba4e83acf0d1ba075a7893","is_oa":true,"landing_page_url":"https://doaj.org/article/0de565c5f8ba4e83acf0d1ba075a7893","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","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-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PLoS Computational Biology, Vol 11, Iss 4, p e1004207 (2015)","raw_type":"article"},{"id":"pmh:oai:europepmc.org:3382680","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4407897","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","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Text"},{"id":"pmh:oai:figshare.com:article/1392334","is_oa":true,"landing_page_url":"https://figshare.com/articles/dataset/_Thermal_Stabilization_of_Dihydrofolate_Reductase_Using_Monte_Carlo_Unfolding_Simulations_and_Its_Functional_Consequences_/1392334","pdf_url":null,"source":{"id":"https://openalex.org/S4306402621","display_name":"INDIGO (University of Illinois at Chicago)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I39422238","host_organization_name":"University of Illinois Chicago","host_organization_lineage":["https://openalex.org/I39422238"],"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"}],"best_oa_location":{"id":"doi:10.1371/journal.pcbi.1004207","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1004207","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004207&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":[],"awards":[{"id":"https://openalex.org/G1172366676","display_name":null,"funder_award_id":"2013AA102804","funder_id":"https://openalex.org/F4320335773","funder_display_name":"National High-tech Research and Development Program"},{"id":"https://openalex.org/G2980910840","display_name":null,"funder_award_id":"R01 GM06870","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G7056232824","display_name":null,"funder_award_id":"T32 GM008313","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320335773","display_name":"National High-tech Research and Development Program","ror":null},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2043205949.pdf","grobid_xml":"https://content.openalex.org/works/W2043205949.grobid-xml"},"referenced_works_count":77,"referenced_works":["https://openalex.org/W319310461","https://openalex.org/W1530704185","https://openalex.org/W1607931568","https://openalex.org/W1973897761","https://openalex.org/W1974027664","https://openalex.org/W1974105492","https://openalex.org/W1981673913","https://openalex.org/W1985006546","https://openalex.org/W1989300794","https://openalex.org/W1990700294","https://openalex.org/W1992579032","https://openalex.org/W1996320633","https://openalex.org/W1998885514","https://openalex.org/W2003057311","https://openalex.org/W2005279391","https://openalex.org/W2005455051","https://openalex.org/W2008440654","https://openalex.org/W2009868245","https://openalex.org/W2011343696","https://openalex.org/W2016019576","https://openalex.org/W2017819155","https://openalex.org/W2024035897","https://openalex.org/W2029871341","https://openalex.org/W2034078233","https://openalex.org/W2040008731","https://openalex.org/W2041467022","https://openalex.org/W2048059266","https://openalex.org/W2049558868","https://openalex.org/W2052234349","https://openalex.org/W2056053449","https://openalex.org/W2058601741","https://openalex.org/W2067608620","https://openalex.org/W2069813219","https://openalex.org/W2070555657","https://openalex.org/W2075032384","https://openalex.org/W2076713412","https://openalex.org/W2081781433","https://openalex.org/W2083144176","https://openalex.org/W2084638727","https://openalex.org/W2087002090","https://openalex.org/W2091415081","https://openalex.org/W2092189458","https://openalex.org/W2093847279","https://openalex.org/W2099672241","https://openalex.org/W2099792341","https://openalex.org/W2101447754","https://openalex.org/W2102388964","https://openalex.org/W2104108767","https://openalex.org/W2106157551","https://openalex.org/W2109441358","https://openalex.org/W2111878373","https://openalex.org/W2115272113","https://openalex.org/W2115503115","https://openalex.org/W2115553515","https://openalex.org/W2117694142","https://openalex.org/W2118265845","https://openalex.org/W2123687265","https://openalex.org/W2124307758","https://openalex.org/W2124433471","https://openalex.org/W2132926880","https://openalex.org/W2134062490","https://openalex.org/W2146606022","https://openalex.org/W2149580316","https://openalex.org/W2150981663","https://openalex.org/W2151601961","https://openalex.org/W2154833904","https://openalex.org/W2157362913","https://openalex.org/W2161859154","https://openalex.org/W2168749685","https://openalex.org/W2169225803","https://openalex.org/W2171741848","https://openalex.org/W2408992651","https://openalex.org/W2474467990","https://openalex.org/W2609912642","https://openalex.org/W3037896947","https://openalex.org/W4211196614","https://openalex.org/W6721156154"],"related_works":["https://openalex.org/W2014611904","https://openalex.org/W1993736519","https://openalex.org/W2413337078","https://openalex.org/W2129112116","https://openalex.org/W2052503234","https://openalex.org/W2046209300","https://openalex.org/W2469117579","https://openalex.org/W2045828736","https://openalex.org/W2099128918","https://openalex.org/W1973106905"],"abstract_inverted_index":{"Design":[0],"of":[1,24,47,86,93,107,123,146,161,180,190,193,215],"proteins":[2,255],"with":[3,64,240],"desired":[4],"thermal":[5,207],"properties":[6],"is":[7,45,174],"important":[8,159],"for":[9,111,136,187,219,250],"scientific":[10],"and":[11,58,67,95,114,127,132,139,150,209,252],"biotechnological":[12],"applications.":[13],"Here":[14],"we":[15,59,80,197,229],"developed":[16],"a":[17,35,83,90,119,199,216,231,267],"theoretical":[18,62],"approach":[19],"to":[20,55,270],"predict":[21],"the":[22,147,158,177,181,188,194,213],"effect":[23],"mutations":[25,191,224],"on":[26,39,75,261],"protein":[27,164],"stability":[28,208],"from":[29],"non-equilibrium":[30],"unfolding":[31,78,133,262],"simulations.":[32],"We":[33,117],"establish":[34],"relative":[36],"measure":[37],"based":[38,74,260],"apparent":[40],"simulated":[41],"melting":[42,130],"temperatures":[43,131],"that":[44,257],"independent":[46],"simulation":[48],"length":[49],"and,":[50],"under":[51],"certain":[52],"assumptions,":[53],"proportional":[54],"equilibrium":[56],"stability,":[57],"justify":[60],"this":[61],"development":[63],"extensive":[65],"simulations":[66,263],"experimental":[68,115,151],"data.":[69],"Using":[70],"our":[71,227],"new":[72],"method":[73,99],"all-atom":[76],"Monte-Carlo":[77],"simulations,":[79],"carried":[81],"out":[82],"saturating":[84],"mutagenesis":[85],"Dihydrofolate":[87],"Reductase":[88],"(DHFR),":[89],"key":[91],"target":[92],"antibiotics":[94],"chemotherapeutic":[96],"drugs.":[97],"The":[98,142,166],"predicted":[100,126,225],"more":[101],"than":[102,246],"500":[103],"stabilizing":[104,168,223,272],"mutations,":[105],"several":[106,253],"which":[108,173],"were":[109],"selected":[110],"detailed":[112],"computational":[113,258],"analysis.":[116],"find":[118],"highly":[120,232],"significant":[121,203],"correlation":[122,143,205],"r=0.65-0.68":[124],"between":[125,144,206],"experimentally":[128],"determined":[129],"denaturant":[134],"concentrations":[135],"WT":[137],"DHFR":[138,238,251],"42":[140],"mutants.":[141],"energy":[145],"native":[148],"state":[149],"denaturation":[152,242],"temperature":[153,243],"was":[154,171],"much":[155],"weaker,":[156],"indicating":[157,212],"role":[160],"entropy":[162],"in":[163,176],"stability.":[165],"most":[167],"point":[169],"mutation":[170],"D27F,":[172],"located":[175],"active":[178,195,235],"site":[179,196],"protein,":[182],"rendering":[183],"it":[184],"inactive.":[185],"However":[186],"rest":[189],"outside":[192],"observed":[198],"weak":[200],"yet":[201],"statistically":[202],"positive":[204],"catalytic":[210],"activity":[211],"lack":[214],"stability-activity":[217],"tradeoff":[218],"DHFR.":[220],"By":[221],"combining":[222],"by":[226],"method,":[228],"created":[230],"stable":[233],"catalytically":[234],"E.":[236],"coli":[237],"mutant":[239],"measured":[241],"7.2\u00b0C":[244],"higher":[245],"WT.":[247],"Prediction":[248],"results":[249],"other":[254],"indicate":[256],"approaches":[259],"are":[264],"useful":[265],"as":[266],"general":[268],"technique":[269],"discover":[271],"mutations.":[273]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":3},{"year":2023,"cited_by_count":1},{"year":2022,"cited_by_count":3},{"year":2021,"cited_by_count":3},{"year":2020,"cited_by_count":5},{"year":2019,"cited_by_count":7},{"year":2018,"cited_by_count":3},{"year":2017,"cited_by_count":5},{"year":2016,"cited_by_count":8},{"year":2015,"cited_by_count":1}],"updated_date":"2026-07-25T15:57:00.446498","created_date":"2025-10-10T00:00:00"}