Design of novel repeat proteins

Fabio Parmeggiani
University of Washington
Friday, February 27, 2015
Teer 115 | 2:00pm

Repeat proteins are characterized by imperfect tandem sequence repeats, which often fold into solenoid-like structures. These modular proteins and their idealized versions have attracted interest as binding molecules and biomaterial building blocks, but their versatility has been limited by the available architectures. Therefore, we devised an automated computational approach to design de novo repeat proteins with desired characteristics, exploring geometries beyond the ones observed in known repeat protein families. To assess the robustness of our method, we experimentally tested 83 designed alpha solenoid proteins with a wide range of geometrical parameters. More than 40% were soluble, monomeric, stable at high temperature and corresponded to the original designs, as shown by small angle X ray scattering and crystallography. The success rate of our approach has shown that it is possible to build novel protein architectures in an automated fashion, allowing, in the near future, the high throughput design of new repeat proteins tailored for specific applications.