DiMaio, FrankAdams, Carson2022-04-192022-04-192022-04-192022Adams_washington_0250O_23996.pdfhttp://hdl.handle.net/1773/48447Thesis (Master's)--University of Washington, 2022Low-resolution limitations have long plagued cryo-EM de novo modeling. To address this challenge, I modified Rosetta de novo to incorporate fragments with tertiary context, or nonlocal fragments. Limitations I identified led me to develop a novel method for low-resolution structure determination, combining density and predicted restraints. I used my pipeline to solve and publish two difficult structures, and show it can handle modeling homologous conformers better than attention-based deep-learning methods, AlphaFold and RosettaFold.application/pdfen-USnoneBiochemistryBiological chemistryThesis