Baker, DavidChidyausiku, Tamuka Martin2019-08-142019-08-142019Chidyausiku_washington_0250E_19998.pdfhttp://hdl.handle.net/1773/44054Thesis (Ph.D.)--University of Washington, 2019Active sites and ligand-binding cavities in native proteins are often formed by curved β sheets, and the ability to control β-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Toward this end, we investigated the mechanisms controlling β-sheet curvature by studying the geometry of β sheets in naturally occurring protein structures and folding simulations and defined principles for design. We use these rules to de novo design jellyroll structures with double-stranded β- helices formed by eight antiparallel β-strands. The nuclear magnetic resonance structure of a hyper-thermostable design closely matched the computational model, demonstrating accurate control over the β-sheet structure and loop geometry. Our results open the door to the design of a broad range of non-local β-sheet protein structures like the immunoglobulines which among others are predominant in their role as antibodies.application/pdfen-USCC BYde novojellyrollnanobodiesNFT2BiochemistryBiological chemistryThesis