De novo design of protein binders as functional therapeutics

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.

Author dc:creator

• Huang, Buwei

Advisor dc:contributor.advisor

• Baker, David

• Bioengineering

Statement dc:rights

• CC BY-NC-ND

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/1773/51089

OAI identifier oai:identifier

oai:digital.lib.washington.edu:1773/51089