Computational design of nanoscale rotational mechanics in de novo protein assemblies

Courbet, A.; Hansen, J. P.; Hsia, Y.; Bethel, N.; Park, Y.-J.; Xu, C.; Moyer, A.; Boyken, S. E.; Ueda, G.; Nattermann, U.; Nagarajan, D.; Silva, D.; Sheffler, W.; Quispe, J.; King, N. P.; Bradley, P. H.; Veesler, D.; Kollman, J. M.; Baker, D.

doi:10.1101/2021.11.11.468255

bioRxiv · 10.1101/2021.11.11.468255

Computational design of nanoscale rotational mechanics in de novo protein assemblies

Courbet, A.·Hansen, J. P.·Hsia, Y.·Bethel, N.·Park, Y.-J.·Xu, C.·Moyer, A.·Boyken, S. E.·Ueda, G.·Nattermann, U.·Nagarajan, D.·Silva, D.·Sheffler, W.·Quispe, J.·King, N. P.·Bradley, P. H.·Veesler, D.·Kollman, J. M.·Baker, D.

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Abstract

Natural nanomachines like the F1/F0-ATPase contain protein components that undergo rotation relative to each other. Designing such mechanically constrained nanoscale protein architectures with internal degrees of freedom is an outstanding challenge for computational protein design. Here we explore the de novo construction of protein rotary machinery from designed axle and ring components. Using cryoelectron microscopy, we find that axle-ring systems assemble as designed and populate diverse rotational states depending on symmetry match or mismatch and the designed interface energy landscape. These mechanical systems with internal rotational degrees of freedom are a step towards the systematic design of genetically encodable nanomachines. One-Sentence SummaryComputationally designed self-assembling protein rotary machines sample internal degrees of freedom sculpted within the energy landscape.

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Courbet, A., Hansen, J. P., Hsia, Y., Bethel, N., Park, Y.-J., Xu, C., Moyer, A., Boyken, S. E., Ueda, G., Nattermann, U., Nagarajan, D., Silva, D., Sheffler, W., Quispe, J., King, N. P., Bradley, P. H., Veesler, D., Kollman, J. M., Baker, D.. 2021-11-12. Computational design of nanoscale rotational mechanics in de novo protein assemblies. https://doi.org/10.1101/2021.11.11.468255

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