De-novo design of a random protein walker

Can we make complex protein machines from scratch? We used Rossetta to design a random protein walker that moves along a designed protein track.

For the track, we designed micro-meter long fibres and developed a method to rigidly decorate them with arbitrary proteins. The walkers consist of homo-oligomers that reversibly bind the track using heterodimeric feet; we tested multiple heterodimer interfaces for reversibility and designed six walkers with different numbers of feet. Cryo-EM experiments confirmed the structure of the track and walkers. We performed detailed single molecule tracking and kinetics characterisation and found that the walkers diffuse along the track, and that those with more feet diffuse faster. The system represents a tuneable starting point for future powered protein molecular robots.

Preprint by:
Liza Ulčakar, Hao Shen, Eva Rajh, Tadej Satler, Federico Olivieri, Joseph Watson, Yang Hsia, Justin Decarreau, Eric Lynch, Justin Kollman, David Baker, Ajasja Ljubetič