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The bar-hinge motor : A synthetic protein design exploiting conformational switching to achieve directional motility

Small, Lara S.R.; Zuckermann, Martin J.; Sessions, Richard B.; Curmi, Paul M.G.; Linke, Heiner LU ; Forde, Nancy R. and Bromley, Elizabeth H.C. (2019) In New Journal of Physics 21(1).
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
artificial protein motor, langevin dynamics, molecular motors, nanoscale motion, synthetic biology
in
New Journal of Physics
volume
21
issue
1
publisher
IOP Publishing Ltd.
external identifiers
  • scopus:85062542891
ISSN
1367-2630
DOI
10.1088/1367-2630/aaf3ca
language
English
LU publication?
yes
id
ee1a0b0e-ee9a-4ee5-ac6f-b132ca9d3a27
date added to LUP
2019-03-15 12:46:30
date last changed
2019-09-15 05:15:03
@article{ee1a0b0e-ee9a-4ee5-ac6f-b132ca9d3a27,
  abstract     = {<p>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.</p>},
  articleno    = {013002},
  author       = {Small, Lara S.R. and Zuckermann, Martin J. and Sessions, Richard B. and Curmi, Paul M.G. and Linke, Heiner and Forde, Nancy R. and Bromley, Elizabeth H.C.},
  issn         = {1367-2630},
  keyword      = {artificial protein motor,langevin dynamics,molecular motors,nanoscale motion,synthetic biology},
  language     = {eng},
  month        = {01},
  number       = {1},
  publisher    = {IOP Publishing Ltd.},
  series       = {New Journal of Physics},
  title        = {The bar-hinge motor : A synthetic protein design exploiting conformational switching to achieve directional motility},
  url          = {http://dx.doi.org/10.1088/1367-2630/aaf3ca},
  volume       = {21},
  year         = {2019},
}