AlphaFold accurately predicts distinct conformations based on the oligomeric state of a de novo designed protein.

ABSTRACT: Using the molecular modeling program Rosetta, we designed a de novo protein, called SEWN0.1, which binds the heterotrimeric G protein Gα_q. The design is helical, well-folded, and primarily monomeric in solution at a concentration of 10 μM. However, when we solved the crystal structure of SEWN0.1 at 1.9 Å, we observed a dimer in a conformation incompatible with binding Gα_q . Unintentionally, we had designed a protein that adopts alternate conformations depending on its oligomeric state. Recently, there has been tremendous progress in the field of protein structure prediction as new methods in artificial intelligence have been used to predict structures with high accuracy. We were curious if the structure prediction method AlphaFold could predict the structure of SEWN0.

SUBMITTER: Cummins MC 

PROVIDER: S-EPMC9207892 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature