The Bar-Hinge Motor: A synthetic protein design exploiting conformational switching to achieve directional motility

Small, Lara; Zuckermann, Martin; Sessions, Richard; Curmi, Paul; Linke, Heiner; Forde, Nancy; Bromley, Elizabeth

Abstract

One challenge to synthetic biology is to design functional machines from natural building blocks, from individual amino acids up to larger motifs such as the coiled coil. Here we investigate a novel bipedal motor concept, the Bar-Hinge Motor (BHM), a peptide-based motor capable of executing directed motion via externally controlled conformational switching between a straight bar and a V-shaped hinged form. Incorporating ligand-regulated binding to a DNA track and periodic control of ligand supply makes the BHM an example of a 'clocked walker'. Here, we employ a coarse-grained computational model for the BHM to assess the feasibility of a proposed experimental realization, with conformational switching regulated through the photoisomerization of peptide-bound azobenzene molecules. The results of numerical simulations using the model show that the incorporation of this conformational switch is necessary for the BHM to execute directional, rather than random, motion on a one-dimensional track. The power-stroke-driven directed motion is seen in the model even under conditions that underestimate the level of control we expect to be able to produce in the experimental realisation, demonstrating that this type of design should be an excellent vehicle for exploring the physics behind protein motion. By investigating its force-dependent dynamics, we show that the BHM is capable of directional motion against an applied load, even in the more relaxed conformational switching regimes. Thus, BHM appears to be an excellent candidate for a motor design incorporating a power stroke, enabling us to explore the ability of switchable coiled-coil designs to deliver power strokes within synthetic biology.

Citation

Small, L., Zuckermann, M., Sessions, R., Curmi, P., Linke, H., Forde, N., & Bromley, E. (2019). The Bar-Hinge Motor: A synthetic protein design exploiting conformational switching to achieve directional motility. New Journal of Physics, 21, Article 013002. https://doi.org/10.1088/1367-2630/aaf3ca

• Journal Article Type: Article
• Acceptance Date: Nov 26, 2018
• Online Publication Date: Jan 8, 2019
• Publication Date: Jan 8, 2019
• Deposit Date: Nov 22, 2018
• Publicly Available Date: Jan 9, 2019
• Journal: New Journal of Physics
• Electronic ISSN: 1367-2630
• Publisher: IOP Publishing
• Peer Reviewed: Peer Reviewed
• Volume: 21
• Article Number: 013002
• DOI: https://doi.org/10.1088/1367-2630/aaf3ca
• Public URL: https://durham-repository.worktribe.com/output/1342686