{"id":{"repo_id":"washington","oai_identifier":"oai:digital.lib.washington.edu:1773/51089"},"canonical_url":"https://search.dev.ndltd.org/etd/washington/oai:digital.lib.washington.edu:1773/51089","repository":{"repo_id":"washington","name":"University of Washington","base_url":"https://digital.lib.washington.edu/server/oai/request"},"display":{"title":"De novo design of protein binders as functional therapeutics","abstract":"De novo design of protein binding proteins (minibinders) with target structure information alone remains a grand challenge. A general computational design framework includes (1) generation of binder backbones, (2) sequence design and side-chain refinement, (3) resampling, and (4) prediction of binding and evaluation of the minibinders as a monomer. In Chapter 1, I review the improved computational minibinder design method I have contributed to develop. With these cutting-edge pipelines, I describe two strategies of applying designed minibinders as novel functional therapeutics: in Chapter 2, I report the design of minibinder antagonists as immune modulator for cytokine storm; in Chapter 3, I report the design of endocytosis ligands for target degradation and signaling amplification. Overall, the minibinder is a brand-new drug modality/platform with advantages of ultra-stability, high-specificity, robust production, and modularity. The work described indicate the great potential of the minibinder to bridge the gap of existing therapeutics and revolutionize the future of protein drug development.","abstract_html":"De novo design of protein binding proteins (minibinders) with target structure information alone remains a grand challenge. A general computational design framework includes (1) generation of binder backbones, (2) sequence design and side-chain refinement, (3) resampling, and (4) prediction of binding and evaluation of the minibinders as a monomer. In Chapter 1, I review the improved computational minibinder design method I have contributed to develop. With these cutting-edge pipelines, I describe two strategies of applying designed minibinders as novel functional therapeutics: in Chapter 2, I report the design of minibinder antagonists as immune modulator for cytokine storm; in Chapter 3, I report the design of endocytosis ligands for target degradation and signaling amplification. Overall, the minibinder is a brand-new drug modality/platform with advantages of ultra-stability, high-specificity, robust production, and modularity. The work described indicate the great potential of the minibinder to bridge the gap of existing therapeutics and revolutionize the future of protein drug development.","abstract_has_math":false,"creators":["Huang, Buwei"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Baker, David"],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-02-12","date_published":"2024-02-12","updated_at":"2026-07-24T05:58:27Z","subjects":["Bioengineering"],"languages":["en_US"],"rights":["CC BY-NC-ND"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1773/51089","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Baker, David"]},{"key":"dc:creator","label":"Author","values":["Huang, Buwei"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-02-12T23:38:46Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-02-12"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Bioengineering"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]},{"key":"dc:rights","label":"Dc Rights","values":["CC BY-NC-ND"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["Huang_washington_0250E_26275.pdf"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1773/51089"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Thesis (Ph.D.)--University of Washington, 2023"]},{"key":"dc:description.abstract","label":"Abstract","values":["De novo design of protein binding proteins (minibinders) with target structure information alone remains a grand challenge. A general computational design framework includes (1) generation of binder backbones, (2) sequence design and side-chain refinement, (3) resampling, and (4) prediction of binding and evaluation of the minibinders as a monomer. In Chapter 1, I review the improved computational minibinder design method I have contributed to develop. With these cutting-edge pipelines, I describe two strategies of applying designed minibinders as novel functional therapeutics: in Chapter 2, I report the design of minibinder antagonists as immune modulator for cytokine storm; in Chapter 3, I report the design of endocytosis ligands for target degradation and signaling amplification. Overall, the minibinder is a brand-new drug modality/platform with advantages of ultra-stability, high-specificity, robust production, and modularity. The work described indicate the great potential of the minibinder to bridge the gap of existing therapeutics and revolutionize the future of protein drug development."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["De novo design of protein binders as functional therapeutics"]}]}],"canonical_facts":{"dc:contributor.advisor":["Baker, David"],"dc:creator":["Huang, Buwei"],"dc:date.accessioned":["2024-02-12T23:38:46Z"],"dc:date.issued":["2024-02-12"],"dc:description":["Thesis (Ph.D.)--University of Washington, 2023"],"dc:description.abstract":["De novo design of protein binding proteins (minibinders) with target structure information alone remains a grand challenge. A general computational design framework includes (1) generation of binder backbones, (2) sequence design and side-chain refinement, (3) resampling, and (4) prediction of binding and evaluation of the minibinders as a monomer. In Chapter 1, I review the improved computational minibinder design method I have contributed to develop. With these cutting-edge pipelines, I describe two strategies of applying designed minibinders as novel functional therapeutics: in Chapter 2, I report the design of minibinder antagonists as immune modulator for cytokine storm; in Chapter 3, I report the design of endocytosis ligands for target degradation and signaling amplification. Overall, the minibinder is a brand-new drug modality/platform with advantages of ultra-stability, high-specificity, robust production, and modularity. The work described indicate the great potential of the minibinder to bridge the gap of existing therapeutics and revolutionize the future of protein drug development."],"dc:format.mimetype":["application/pdf"],"dc:identifier.other":["Huang_washington_0250E_26275.pdf"],"dc:identifier.uri":["http://hdl.handle.net/1773/51089"],"dc:language.iso":["en_US"],"dc:rights":["CC BY-NC-ND"],"dc:subject":["Bioengineering"],"dc:title":["De novo design of protein binders as functional therapeutics"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T05:58:27Z"}