{"id":"https://openalex.org/W7222921680","doi":"https://doi.org/10.64898/2026.10.16.759603","title":"Exploring the Design Space of 3 10 -helical Bundles using Non-canonical Amino Acids","display_name":"Exploring the Design Space of 3 10 -helical Bundles using Non-canonical Amino Acids","publication_year":2026,"publication_date":"2026-10-19","ids":{"openalex":"https://openalex.org/W7222921680","doi":"https://doi.org/10.64898/2026.10.16.759603"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.16.759603","doi":"https://doi.org/10.64898/2026.10.16.759603","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.16.759603","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/19/2026.10.16.759603.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/19/2026.10.16.759603.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5023874985","display_name":"Xiyue Leng","orcid":"https://orcid.org/0000-0002-4441-2352","observed_orcids":["https://orcid.org/0000-0002-4441-2352"]},"institutions":[{"id":"https://openalex.org/I36234482","display_name":"University of Bristol","ror":"https://ror.org/0524sp257","country_code":"GB","type":"education","lineage":["https://openalex.org/I36234482"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Xiyue Leng","raw_affiliation_strings":["School of Chemistry, University of Bristol, Bristol, UK"],"raw_orcid":"https://orcid.org/0000-0002-4441-2352","affiliations":[{"raw_affiliation_string":"School of Chemistry, University of Bristol, Bristol, UK","institution_ids":["https://openalex.org/I36234482"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5079804629","display_name":"Jonathan Clayden","orcid":"https://orcid.org/0000-0001-5080-9535","observed_orcids":["https://orcid.org/0000-0001-5080-9535"]},"institutions":[{"id":"https://openalex.org/I36234482","display_name":"University of Bristol","ror":"https://ror.org/0524sp257","country_code":"GB","type":"education","lineage":["https://openalex.org/I36234482"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Jonathan Clayden","raw_affiliation_strings":["School of Chemistry, University of Bristol, Bristol, UK"],"raw_orcid":"https://orcid.org/0000-0001-5080-9535","affiliations":[{"raw_affiliation_string":"School of Chemistry, University of Bristol, Bristol, UK","institution_ids":["https://openalex.org/I36234482"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5023900250","display_name":"Derek N. Woolfson","orcid":"https://orcid.org/0000-0002-0394-3202","observed_orcids":["https://orcid.org/0000-0002-0394-3202"]},"institutions":[{"id":"https://openalex.org/I124055696","display_name":"University of Copenhagen","ror":"https://ror.org/035b05819","country_code":"DK","type":"education","lineage":["https://openalex.org/I124055696"]},{"id":"https://openalex.org/I2801134892","display_name":"Novo Nordisk Foundation","ror":"https://ror.org/04txyc737","country_code":"DK","type":"facility","lineage":["https://openalex.org/I2801134892"]},{"id":"https://openalex.org/I36234482","display_name":"University of Bristol","ror":"https://ror.org/0524sp257","country_code":"GB","type":"education","lineage":["https://openalex.org/I36234482"]},{"id":"https://openalex.org/I4210149754","display_name":"Max Planck-Bristol Centre for Minimal Biology","ror":"https://ror.org/05k0x2619","country_code":"GB","type":"facility","lineage":["https://openalex.org/I149899117","https://openalex.org/I36234482","https://openalex.org/I4210149754"]}],"countries":["DK","GB"],"is_corresponding":true,"raw_author_name":"Derek N. Woolfson","raw_affiliation_strings":["Max Planck-Bristol Centre for Minimal Biology, University of Bristol, Bristol, UK","Novo Nordisk Foundation Center for Protein Design, Department of Biology and Department of Drug Design and Pharmacology, University of Copenhagen, DK","School of Biochemistry, University of Bristol, Medical Sciences Building, Bristol, UK","School of Chemistry, University of Bristol, Bristol, UK"],"raw_orcid":"https://orcid.org/0000-0002-0394-3202","affiliations":[{"raw_affiliation_string":"Max Planck-Bristol Centre for Minimal Biology, University of Bristol, Bristol, UK","institution_ids":["https://openalex.org/I36234482","https://openalex.org/I4210149754"]},{"raw_affiliation_string":"Novo Nordisk Foundation Center for Protein Design, Department of Biology and Department of Drug Design and Pharmacology, University of Copenhagen, DK","institution_ids":["https://openalex.org/I124055696","https://openalex.org/I2801134892"]},{"raw_affiliation_string":"School of Biochemistry, University of Bristol, Medical Sciences Building, Bristol, UK","institution_ids":["https://openalex.org/I36234482"]},{"raw_affiliation_string":"School of Chemistry, University of Bristol, Bristol, UK","institution_ids":["https://openalex.org/I36234482"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5023900250"],"corresponding_institution_ids":["https://openalex.org/I124055696","https://openalex.org/I2801134892","https://openalex.org/I36234482","https://openalex.org/I4210149754"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.5336999893188477,"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":0.5336999893188477,"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/T10911","display_name":"Chemical Synthesis and Analysis","score":0.4578000009059906,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T13326","display_name":"Biochemical and Structural Characterization","score":0.001500000013038516,"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/310-helix","display_name":"310-helix","score":0.7910000085830688},{"id":"https://openalex.org/keywords/unnatural-amino-acids","display_name":"unnatural amino acids","score":0.9350000023841858},{"id":"https://openalex.org/keywords/1-aminocyclopropane-1-carboxylic-acid","display_name":"1-aminocyclopropane-1-carboxylic acid","score":0.9700000286102295},{"id":"https://openalex.org/keywords/de-novo-peptide-design","display_name":"de novo peptide design","score":0.9419999718666077},{"id":"https://openalex.org/keywords/sequence-constraints","display_name":"sequence constraints","score":0.640999972820282},{"id":"https://openalex.org/keywords/hydrophobic-core","display_name":"hydrophobic core","score":0.8330000042915344},{"id":"https://openalex.org/keywords/cyclic-amino-acids","display_name":"cyclic amino acids","score":0.6240000128746033},{"id":"https://openalex.org/keywords/dye-binding","display_name":"dye binding","score":0.5830000042915344},{"id":"https://openalex.org/keywords/hydrophobic-cavity","display_name":"hydrophobic cavity","score":0.7369999885559082}],"concepts":[{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.7534000277519226},{"id":"https://openalex.org/C201194858","wikidata":"https://www.wikidata.org/wiki/Q898238","display_name":"Steric effects","level":2,"score":0.7084000110626221},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.609000027179718},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5979999899864197},{"id":"https://openalex.org/C30711495","wikidata":"https://www.wikidata.org/wiki/Q289411","display_name":"Sequence space","level":3,"score":0.5638999938964844},{"id":"https://openalex.org/C152769699","wikidata":"https://www.wikidata.org/wiki/Q410814","display_name":"Protein design","level":3,"score":0.5180000066757202},{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.49470001459121704},{"id":"https://openalex.org/C167625842","wikidata":"https://www.wikidata.org/wiki/Q899763","display_name":"Peptide sequence","level":3,"score":0.428600013256073},{"id":"https://openalex.org/C2778530040","wikidata":"https://www.wikidata.org/wiki/Q1937315","display_name":"Helix (gastropod)","level":3,"score":0.396699994802475},{"id":"https://openalex.org/C2779200411","wikidata":"https://www.wikidata.org/wiki/Q80250","display_name":"Cyclopropane","level":3,"score":0.3598000109195709},{"id":"https://openalex.org/C2779856020","wikidata":"https://www.wikidata.org/wiki/Q218642","display_name":"Alanine","level":3,"score":0.33399999141693115},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.33309999108314514},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.3246999979019165},{"id":"https://openalex.org/C2994376932","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Amino acid residue","level":4,"score":0.31619998812675476},{"id":"https://openalex.org/C2778134712","wikidata":"https://www.wikidata.org/wiki/Q1047307","display_name":"Bundle","level":2,"score":0.3154999911785126},{"id":"https://openalex.org/C90260826","wikidata":"https://www.wikidata.org/wiki/Q899157","display_name":"Hydrophobic effect","level":2,"score":0.3075000047683716},{"id":"https://openalex.org/C203087120","wikidata":"https://www.wikidata.org/wiki/Q372229","display_name":"Helix bundle","level":3,"score":0.2994000017642975},{"id":"https://openalex.org/C2776196297","wikidata":"https://www.wikidata.org/wiki/Q17138781","display_name":"Twist","level":2,"score":0.2985000014305115},{"id":"https://openalex.org/C8010536","wikidata":"https://www.wikidata.org/wiki/Q160398","display_name":"Crystallography","level":1,"score":0.29319998621940613},{"id":"https://openalex.org/C85641259","wikidata":"https://www.wikidata.org/wiki/Q290042","display_name":"Turn (biochemistry)","level":2,"score":0.2847999930381775},{"id":"https://openalex.org/C2164484","wikidata":"https://www.wikidata.org/wiki/Q5170150","display_name":"Core (optical fiber)","level":2,"score":0.2623000144958496},{"id":"https://openalex.org/C2779281246","wikidata":"https://www.wikidata.org/wiki/Q172847","display_name":"Peptide","level":2,"score":0.2500999867916107}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.10.16.759603","doi":"https://doi.org/10.64898/2026.10.16.759603","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.16.759603","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/19/2026.10.16.759603.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.10.16.759603","doi":"https://doi.org/10.64898/2026.10.16.759603","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.16.759603","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/19/2026.10.16.759603.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G1417047297","display_name":null,"funder_award_id":"EP/S024107","funder_id":"https://openalex.org/F4320334627","funder_display_name":"Engineering and Physical Sciences Research Council"},{"id":"https://openalex.org/G6012208388","display_name":"EPSRC Centre for Doctoral Training in Technology Enhanced Chemical Synthesis","funder_award_id":"EP/S024107/1","funder_id":"https://openalex.org/F4320334627","funder_display_name":"Engineering and Physical Sciences Research Council"},{"id":"https://openalex.org/G7930062281","display_name":"Core Capability for Chemistry Research - Strategic Investment in Mass Spectrometry","funder_award_id":"EP/K03927X/1","funder_id":"https://openalex.org/F4320334627","funder_display_name":"Engineering and Physical Sciences Research Council"}],"funders":[{"id":"https://openalex.org/F4320313096","display_name":"Diamond Light Source","ror":"https://ror.org/05etxs293"},{"id":"https://openalex.org/F4320320360","display_name":"University of Bristol","ror":"https://ror.org/0524sp257"},{"id":"https://openalex.org/F4320322436","display_name":"Novo Nordisk","ror":"https://ror.org/0435rc536"},{"id":"https://openalex.org/F4320325957","display_name":"Novo Nordisk Fonden","ror":"https://ror.org/04txyc737"},{"id":"https://openalex.org/F4320334627","display_name":"Engineering and Physical Sciences Research Council","ror":"https://ror.org/0439y7842"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7222921680.pdf","grobid_xml":"https://content.openalex.org/works/W7222921680.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7212365085","https://openalex.org/W4200228711","https://openalex.org/W4283372224","https://openalex.org/W2034950498","https://openalex.org/W2894558186","https://openalex.org/W1598905143","https://openalex.org/W4414371735","https://openalex.org/W2286619141","https://openalex.org/W1996919464","https://openalex.org/W2170819359"],"abstract_inverted_index":{"Abstract":[0],"Steric":[1],"constraints":[2,261],"and":[3,10,21,69,89,95,114,126,143,238,269],"favored":[4],"hydrogen-bonding":[5],"patterns":[6],"result":[7],"in":[8],"peptides":[9],"proteins":[11],"based":[12,46],"on":[13,48],"\u03b1-amino":[14],"acids":[15,37],"being":[16],"largely":[17,202],"confined":[18],"to":[19,117,218,234,272],"\u03b1-helical":[20],"\u03b2-strand":[22],"secondary":[23],"structures.":[24],"Although":[25],"stand-alone":[26],"3":[27,71,91,148,171,175,243,265],"10":[28,72,92,149,176,244,266],"helices":[29],"can":[30],"be":[31],"stabilized":[32],"by":[33],"incorporating":[34],"\u03b1,\u03b1-disubstituted":[35],"amino":[36,135],"such":[38],"as":[39],"amino-isobutyric":[40],"acid":[41,136,138,169,207],"(Aib,":[42],"U":[43],"),":[44],"assemblies":[45],"solely":[47],"this":[49,87,119],"structure":[50],"are":[51,140],"rare.":[52],"Previously,":[53],"we":[54,107],"reported":[55],"a":[56,79,174],"de":[57,263],"novo":[58,264],"designed":[59],"peptide,":[60],"(":[61,221],"ELUULK":[62,222],")":[63,223],"4":[64],",":[65,225],"that":[66,252],"forms":[67],"stable":[68,147],"defined":[70],"-helical":[73,150,177,245,267],"bundles.":[74,105],"The":[75],"Leu":[76,195],"residues":[77,85,98],"create":[78,249],"consolidated":[80],"hydrophobic":[81,193,250],"core,":[82],"the":[83,96,100,104,109,132,158,165,191,216,229],"Aib":[84,156],"flank":[86],"core":[88,232],"promote":[90],"-helix":[93],"formation,":[94],"Glu/Lys":[97],"define":[99,259],"water-soluble":[101],"surface":[102],"of":[103,111,124,155,228,240],"Here,":[106],"examine":[108],"mutability":[110],"these":[112,257],"sites":[113],"their":[115,273],"contributions":[116],"maintaining":[118],"unusual":[120],"fold.":[121],"Surface":[122],"substitutions":[123,185],"Glu":[125],"Lys":[127],"with":[128,180],"Asp,":[129],"Arg,":[130],"or":[131,236],"cyclic":[133],"non-canonical":[134],"4-aminopiperidine-4-carboxylic":[137],"(Api)":[139],"well":[141],"tolerated,":[142],"all":[144],"variants":[145,248],"form":[146],"oligomers.":[151],"In":[152],"contrast,":[153],"mutation":[154,227],"at":[157],"flanking":[159],"positions":[160,233],"reveals":[161],"strong":[162],"constraints:":[163],"only":[164],"cyclopropane":[166],"analogue,":[167],"1-aminocyclopropane-1-carboxylic":[168],"(Ac":[170,208],"c),":[172],"preserves":[173],"bundle,":[178],"albeit":[179],"reduced":[181],"thermal":[182],"stability.":[183],"Core":[184],"prove":[186],"even":[187],"more":[188],"restrictive.":[189],"Of":[190],"proteinogenic":[192],"residues,":[194],"uniquely":[196],"supports":[197],"bundle":[198],"formation.":[199],"Cyclic":[200],"analogues":[201],"disrupt":[203],"assembly,":[204],"although":[205],"1-aminocyclopentane-1-carboxylic":[206],"5":[209],"c)":[210],"is":[211],"partially":[212],"tolerated.":[213],"However,":[214],"extending":[215],"design":[217],"seven":[219],"hexads,":[220],"7":[224],"enables":[226],"two":[230],"central":[231],"Ala":[235],"Gly":[237],"retention":[239],"stable,":[241],"hexameric":[242],"assemblies.":[246],"These":[247],"cavities":[251],"bind":[253],"environment-sensitive":[254],"dyes.":[255],"Together,":[256],"studies":[258],"sequence":[260],"for":[262],"bundles":[268],"establish":[270],"routes":[271],"functionalization.":[274]},"counts_by_year":[],"updated_date":"2026-11-08T12:12:28.789561","created_date":"2026-10-20T00:00:00"}