Using Synthetic Biology to Show a Continuity of Sequence Similarity Between Seemingly Unrelated Protein Superfamilies

Science Center, Bent Corridor

Classifying protein domains allows researchers to understand the relationships and commonalities between them. Protein domains in the same fold posses the same major secondary structures in the same arrangement. Domains in the same superfamily possess low sequence identity but have common structures and functional features. These properties suggest that domains within the same superfamily possibly have a common evolutionary origin. Some researchers believe that protein domains in the same fold also have a common evolutionary origin, but this claim has been untestable. My research with Aaron Goldman addresses this issue by computationally examining the classification of failed evolutionary variations of domains. We used the program Rosetta Design, which was created for nanotechnology and pharmacology, to simulate evolution. The program takes in a desired protein structure and outputs a synthetic sequence that will fold into that structure. Our preliminary results show that if they existed in nature, some of the synthetic amino acid sequences in the same fold but in separate superfamilies would share a high sequence similarity (above 35%) with each other and with natural domains. In conclusion, these preliminary results indicate that protein domains from separate superfamilies might share a common evolutionary origin and that the separate superfamilies should be combined into a single larger superfamily. It could also imply that some domains from the same fold share a common evolutionary origin.