{"id":"https://openalex.org/W1985563952","doi":"https://doi.org/10.1371/journal.pcbi.1000627","title":"Tradeoff Between Stability and Multispecificity in the Design of Promiscuous Proteins","display_name":"Tradeoff Between Stability and Multispecificity in the Design of Promiscuous Proteins","publication_year":2009,"publication_date":"2009-12-23","ids":{"openalex":"https://openalex.org/W1985563952","doi":"https://doi.org/10.1371/journal.pcbi.1000627","mag":"1985563952","pmid":"https://pubmed.ncbi.nlm.nih.gov/20041208"},"language":"en","primary_location":{"id":"doi:10.1371/journal.pcbi.1000627","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1000627","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1000627&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.1000627&type=printable","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5051946088","display_name":"Menachem Fromer","orcid":"https://orcid.org/0000-0003-3749-4342"},"institutions":[{"id":"https://openalex.org/I197251160","display_name":"Hebrew University of Jerusalem","ror":"https://ror.org/03qxff017","country_code":"IL","type":"education","lineage":["https://openalex.org/I197251160"]}],"countries":["IL"],"is_corresponding":false,"raw_author_name":"Menachem Fromer","raw_affiliation_strings":["School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel"],"affiliations":[{"raw_affiliation_string":"School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel","institution_ids":["https://openalex.org/I197251160"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5004000734","display_name":"Julia M. Shifman","orcid":"https://orcid.org/0000-0001-6678-6497"},"institutions":[{"id":"https://openalex.org/I197251160","display_name":"Hebrew University of Jerusalem","ror":"https://ror.org/03qxff017","country_code":"IL","type":"education","lineage":["https://openalex.org/I197251160"]}],"countries":["IL"],"is_corresponding":true,"raw_author_name":"Julia M. Shifman","raw_affiliation_strings":["Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel","Department of Biological Chemistry The Alexander Silberman Institute of Life Sciences The Hebrew University of Jerusalem Jerusalem Israel"],"affiliations":[{"raw_affiliation_string":"Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel","institution_ids":["https://openalex.org/I197251160"]},{"raw_affiliation_string":"Department of Biological Chemistry The Alexander Silberman Institute of Life Sciences The Hebrew University of Jerusalem Jerusalem Israel","institution_ids":["https://openalex.org/I197251160"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5004000734"],"corresponding_institution_ids":["https://openalex.org/I197251160"],"apc_list":{"value":2655,"currency":"USD","value_usd":2655},"apc_paid":{"value":2655,"currency":"USD","value_usd":2655},"fwci":2.2916,"has_fulltext":true,"cited_by_count":64,"citation_normalized_percentile":{"value":0.87682828,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":99},"biblio":{"volume":"5","issue":"12","first_page":"e1000627","last_page":"e1000627"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9997000098228455,"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":0.9997000098228455,"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":0.9972000122070312,"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/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.996399998664856,"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/computational-biology","display_name":"Computational biology","score":0.5803819894790649},{"id":"https://openalex.org/keywords/stability","display_name":"Stability (learning theory)","score":0.548143744468689},{"id":"https://openalex.org/keywords/sequence","display_name":"Sequence (biology)","score":0.5291129946708679},{"id":"https://openalex.org/keywords/protein-design","display_name":"Protein design","score":0.49760082364082336},{"id":"https://openalex.org/keywords/compromise","display_name":"Compromise","score":0.4733310341835022},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.44692111015319824},{"id":"https://openalex.org/keywords/protein-stability","display_name":"Protein stability","score":0.4402596354484558},{"id":"https://openalex.org/keywords/natural","display_name":"Natural (archaeology)","score":0.41912731528282166},{"id":"https://openalex.org/keywords/sequence-alignment","display_name":"Sequence alignment","score":0.4158025085926056},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.40523266792297363},{"id":"https://openalex.org/keywords/protein-structure","display_name":"Protein structure","score":0.3727361857891083},{"id":"https://openalex.org/keywords/genetics","display_name":"Genetics","score":0.26725369691848755},{"id":"https://openalex.org/keywords/machine-learning","display_name":"Machine learning","score":0.22836098074913025},{"id":"https://openalex.org/keywords/peptide-sequence","display_name":"Peptide sequence","score":0.19547513127326965},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.13507738709449768},{"id":"https://openalex.org/keywords/gene","display_name":"Gene","score":0.11356279253959656}],"concepts":[{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5803819894790649},{"id":"https://openalex.org/C112972136","wikidata":"https://www.wikidata.org/wiki/Q7595718","display_name":"Stability (learning theory)","level":2,"score":0.548143744468689},{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.5291129946708679},{"id":"https://openalex.org/C152769699","wikidata":"https://www.wikidata.org/wiki/Q410814","display_name":"Protein design","level":3,"score":0.49760082364082336},{"id":"https://openalex.org/C46355384","wikidata":"https://www.wikidata.org/wiki/Q726686","display_name":"Compromise","level":2,"score":0.4733310341835022},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.44692111015319824},{"id":"https://openalex.org/C2988375501","wikidata":"https://www.wikidata.org/wiki/Q847556","display_name":"Protein stability","level":2,"score":0.4402596354484558},{"id":"https://openalex.org/C2776608160","wikidata":"https://www.wikidata.org/wiki/Q4785462","display_name":"Natural (archaeology)","level":2,"score":0.41912731528282166},{"id":"https://openalex.org/C45484198","wikidata":"https://www.wikidata.org/wiki/Q827246","display_name":"Sequence alignment","level":4,"score":0.4158025085926056},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.40523266792297363},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.3727361857891083},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.26725369691848755},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.22836098074913025},{"id":"https://openalex.org/C167625842","wikidata":"https://www.wikidata.org/wiki/Q899763","display_name":"Peptide sequence","level":3,"score":0.19547513127326965},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.13507738709449768},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.11356279253959656},{"id":"https://openalex.org/C144024400","wikidata":"https://www.wikidata.org/wiki/Q21201","display_name":"Sociology","level":0,"score":0.0},{"id":"https://openalex.org/C36289849","wikidata":"https://www.wikidata.org/wiki/Q34749","display_name":"Social science","level":1,"score":0.0},{"id":"https://openalex.org/C151730666","wikidata":"https://www.wikidata.org/wiki/Q7205","display_name":"Paleontology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000595","descriptor_name":"Amino Acid Sequence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000595","descriptor_name":"Amino Acid Sequence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000595","descriptor_name":"Amino Acid Sequence","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":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002147","descriptor_name":"Calmodulin","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D002147","descriptor_name":"Calmodulin","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D002147","descriptor_name":"Calmodulin","qualifier_ui":"Q000737","qualifier_name":"chemistry","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":"D003198","descriptor_name":"Computer Simulation","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":"D008969","descriptor_name":"Molecular Sequence Data","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008969","descriptor_name":"Molecular Sequence Data","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008969","descriptor_name":"Molecular Sequence Data","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":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D020539","descriptor_name":"Sequence Analysis, Protein","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":false},{"descriptor_ui":"D020539","descriptor_name":"Sequence Analysis, Protein","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":false},{"descriptor_ui":"D020539","descriptor_name":"Sequence Analysis, Protein","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":false}],"locations_count":5,"locations":[{"id":"doi:10.1371/journal.pcbi.1000627","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1000627","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1000627&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:20041208","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/20041208","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:CiteSeerX.psu:10.1.1.355.7677","is_oa":false,"landing_page_url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.355.7677","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/74/d5/PLoS_Comput_Biol_2009_Dec_24_5(12)_e1000627.tar.gz","raw_type":"text"},{"id":"pmh:oai:doaj.org/article:13532d43757f43e0bf0a0b324b13e726","is_oa":true,"landing_page_url":"https://doaj.org/article/13532d43757f43e0bf0a0b324b13e726","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":"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 5, Iss 12, p e1000627 (2009)","raw_type":"article"},{"id":"pmh:oai:pubmedcentral.nih.gov:2790338","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2790338","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PLoS Comput Biol","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1371/journal.pcbi.1000627","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1000627","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1000627&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":[{"display_name":"Affordable and clean energy","score":0.7400000095367432,"id":"https://metadata.un.org/sdg/7"}],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W1985563952.pdf","grobid_xml":"https://content.openalex.org/works/W1985563952.grobid-xml"},"referenced_works_count":70,"referenced_works":["https://openalex.org/W255996521","https://openalex.org/W1490451576","https://openalex.org/W1597762634","https://openalex.org/W1964215960","https://openalex.org/W1968394750","https://openalex.org/W1971500863","https://openalex.org/W1977871129","https://openalex.org/W1980369656","https://openalex.org/W1987159249","https://openalex.org/W1990338952","https://openalex.org/W1991917050","https://openalex.org/W1996386189","https://openalex.org/W1997436357","https://openalex.org/W1999390565","https://openalex.org/W2003890287","https://openalex.org/W2008620264","https://openalex.org/W2009664421","https://openalex.org/W2010485601","https://openalex.org/W2012852001","https://openalex.org/W2013988051","https://openalex.org/W2016240751","https://openalex.org/W2023370650","https://openalex.org/W2024060531","https://openalex.org/W2024142216","https://openalex.org/W2025221718","https://openalex.org/W2026097048","https://openalex.org/W2026350435","https://openalex.org/W2027189612","https://openalex.org/W2032675793","https://openalex.org/W2035056536","https://openalex.org/W2037511678","https://openalex.org/W2038071582","https://openalex.org/W2046880148","https://openalex.org/W2052366943","https://openalex.org/W2054467356","https://openalex.org/W2061425021","https://openalex.org/W2085497102","https://openalex.org/W2087117183","https://openalex.org/W2091041102","https://openalex.org/W2094392347","https://openalex.org/W2096648003","https://openalex.org/W2100034662","https://openalex.org/W2108781091","https://openalex.org/W2113030357","https://openalex.org/W2115156437","https://openalex.org/W2124307758","https://openalex.org/W2130520896","https://openalex.org/W2130790725","https://openalex.org/W2133380824","https://openalex.org/W2133549457","https://openalex.org/W2135815512","https://openalex.org/W2141042406","https://openalex.org/W2142207967","https://openalex.org/W2142900002","https://openalex.org/W2143630321","https://openalex.org/W2144482528","https://openalex.org/W2145350307","https://openalex.org/W2147466870","https://openalex.org/W2154515666","https://openalex.org/W2158266834","https://openalex.org/W2159291387","https://openalex.org/W2162215949","https://openalex.org/W2165319219","https://openalex.org/W2165594346","https://openalex.org/W2166043581","https://openalex.org/W2168398034","https://openalex.org/W2168749685","https://openalex.org/W4235043210","https://openalex.org/W6609701964","https://openalex.org/W6675196758"],"related_works":["https://openalex.org/W2032675793","https://openalex.org/W1988730649","https://openalex.org/W2026461419","https://openalex.org/W2170120749","https://openalex.org/W2067576503","https://openalex.org/W2199134476","https://openalex.org/W2997244915","https://openalex.org/W2121047544","https://openalex.org/W2170285690","https://openalex.org/W3216044760"],"abstract_inverted_index":{"Natural":[0],"proteins":[1,26,272],"often":[2],"partake":[3],"in":[4,31,188],"several":[5,225],"highly":[6],"specific":[7],"protein-protein":[8],"interactions.":[9],"They":[10],"are":[11,205,217],"thus":[12,181,294],"subject":[13],"to":[14,28,42,72,92,148,219,276],"multiple":[15,297],"opposing":[16],"forces":[17],"during":[18],"evolutionary":[19],"selection.":[20],"To":[21,56],"be":[22,29,199],"functional,":[23],"such":[24,186],"multispecific":[25,65,271],"need":[27,154,161],"stable":[30],"complex":[32],"with":[33,74,102,114,288],"each":[34,103,115],"interaction":[35,101,157,221,249],"partner,":[36],"and,":[37],"at":[38],"the":[39,150,153,160,183,194,208,233,237,246],"same":[40],"time,":[41],"maintain":[43],"affinity":[44,209],"toward":[45],"all":[46,122,211],"partners.":[47],"How":[48],"is":[49],"this":[50,58,240],"multispecificity":[51,252],"acquired":[52],"through":[53],"natural":[54,178],"evolution?":[55],"answer":[57],"compelling":[59],"question,":[60],"we":[61,87,108,140,191],"study":[62],"a":[63,94,262,277,289],"prototypical":[64],"protein,":[66],"calmodulin":[67],"(CaM),":[68],"which":[69],"has":[70,146,282],"evolved":[71],"interact":[73],"hundreds":[75],"of":[76,83,118,185,210,228,239,292],"target":[77],"proteins.":[78],"Starting":[79],"from":[80,265],"high-resolution":[81],"structures":[82],"sixteen":[84,123],"CaM-target":[85,212],"complexes,":[86],"employ":[88],"state-of-the-art":[89],"computational":[90],"methods":[91],"predict":[93],"hundred":[95],"CaM":[96,105,110,131,173,195],"sequences":[97,111,136,174,285],"best":[98],"suited":[99],"for":[100,155,162,168,207,236,286],"individual":[104],"target.":[106],"Then,":[107],"design":[109],"most":[112],"compatible":[113],"possible":[116],"combination":[117],"two,":[119],"three,":[120],"and":[121,137,159,214,251,253],"targets":[124],"simultaneously,":[125],"producing":[126],"almost":[127],"70,000":[128],"low":[129],"energy":[130],"sequences.":[132],"By":[133],"comparing":[134],"these":[135],"their":[138,284,296],"energies,":[139],"gain":[141],"insight":[142],"into":[143,202],"how":[144],"nature":[145],"managed":[147],"find":[149,254],"compromise":[151,234],"between":[152,248],"favorable":[156],"energies":[158],"multispecificity.":[163],"We":[164,223,242,268],"observe":[165],"that":[166,175,193,204,216,231,255,270,281],"designing":[167],"more":[169],"partners":[170],"simultaneously":[171],"yields":[172],"better":[176],"match":[177],"sequence":[179],"profiles,":[180],"emphasizing":[182],"importance":[184],"strategies":[187],"nature.":[189],"Furthermore,":[190],"show":[192],"binding":[196],"interface":[197],"can":[198],"nicely":[200],"partitioned":[201],"positions":[203],"critical":[206],"complexes":[213],"those":[215],"molded":[218],"provide":[220],"specificity.":[222],"reveal":[224],"basic":[226],"categories":[227],"sequence-level":[229],"tradeoffs":[230],"enable":[232],"necessary":[235],"promiscuity":[238],"protein.":[241],"also":[243],"thoroughly":[244],"quantify":[245],"tradeoff":[247],"energetics":[250],"facilitating":[256],"seemingly":[257],"competing":[258],"interactions":[259,287],"requires":[260],"only":[261],"small":[263],"deviation":[264],"optimal":[266],"energies.":[267],"conclude":[269],"have":[273],"been":[274],"subjected":[275],"rigorous":[278],"optimization":[279],"process":[280],"fine-tuned":[283],"precise":[290],"set":[291],"targets,":[293],"conferring":[295],"cellular":[298],"functions.":[299]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2023,"cited_by_count":4},{"year":2022,"cited_by_count":5},{"year":2021,"cited_by_count":3},{"year":2020,"cited_by_count":6},{"year":2019,"cited_by_count":3},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":8},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":5},{"year":2014,"cited_by_count":5},{"year":2013,"cited_by_count":4},{"year":2012,"cited_by_count":6}],"updated_date":"2026-04-21T08:09:41.155169","created_date":"2025-10-10T00:00:00"}