A14 Zeymer: Engineering conformational dynamics of a de novo designed two-domain metalloenzyme

This project aims to turn a de novo designed metalloprotein into an artificial nuclease, in which the interplay of protein function and dynamics can be studied in an evolutionarily unbiased fashion. We plan to re-engineer the hydrophobic dimer interfaces of the two-domain scaffold as well as the domain-connecting flexible loops, such that binding of metal cofactor and substrate leads to conformational transitions and formation of a functional enzyme complex.