The Tumbleweed: Towards a synthetic protein motor

Bromley, Elizabeth H. C.; Kuwada, Nathan J.; Zuckermann, Martin J.; Donadini, Roberta; Samii, Laleh; Blab, Gerhard A.; Gemmen, Gregory J.; López, Benjamín; Curmi, Paul M. G.; Forde, Nancy R.; Woolfson, Derek N.; Linke, Heiner

doi:10.2976/1.3111282

Cited by 38 publications

(60 citation statements)

References 82 publications

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“…The model could be extended to include reverse chemical rate transitions to study the physical mechanism of the recently observed processive backward stepping of myosin V under superstall load forces (26). This type of model could also be used to model the dynamics of molecular motors at filament intersections (27,28), to study the more complex cooperative gating of multiple motors attached to a single cargo (29), or in the design of synthetic molecular motors (30).…”

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confidence: 99%

Mechanochemical model for myosin V

Craig

Linke²

2009

Proc. Natl. Acad. Sci. U.S.A.

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A rigorous numerical test of a hypothetical mechanism of a molecular motor should model explicitly the diffusive motion of the motor's degrees of freedom as well as the transition rates between the motor's chemical states. We present such a Brownian dynamics, mechanochemcial model of the coarse-grain structure of the dimeric, linear motor myosin V. Compared with run-length data, our model provides strong support for a proposed strain-controlled gating mechanism that enhances processivity. We demonstrate that the diffusion rate of a detached motor head during motor stepping is self-consistent with known kinetic rate constants and can explain the motor's key performance features, such as speed and stall force. We present illustrative and realistic animations of motor stepping in the presence of thermal noise. The quantitative success and illustrative power of this type of model suggest that it will be useful in testing our understanding of a range of biological and synthetic motors.Brownian dynamics ͉ molecular motor ͉ strain-dependent gating M yosin V moves cargo through eukaryotic cells by walking in a hand-over-hand fashion along actin filaments (1, 2). Recent high-resolution, single-molecule experiments have provided an unprecedented level of insight into the physical mechanism underlying the coordinated steps of this biological motor. A growing level of support is beginning to form around a hypothetical stepping mechanism in which a step takes place through biased tethered diffusion of a detached head (3-5), and detachment of the two heads is coordinated through intramolecular strain, facilitating hand-over-hand forward stepping and avoiding motor detachment (6-9).One can expect that the realization of such a stepping mechanism should require delicate mutual fine-tuning of the involved chemical rates, the motor's structural and mechanical properties, and the diffusive motion of the motor's degrees of freedom. For example, the rate of tethered diffusion (a function of motor size and stiffness) must be matched to the binding and unbinding rates of the motor head. Furthermore, the effectiveness of a strain-controlled gating mechanism depends on the detailed diffusive motion of the motor's internal degrees of freedom, because intramolecular strain is a quickly varying function of the instantaneous motor conformation.To test the feasibility of a given stepping mechanism of dimeric molecular motors, it is therefore necessary to model the random thermal motion of the molecule's degrees of freedom as well as its mechanical and the kinetic properties. Most suited for this task are so-called ''mechanochemical'' models, which include a discrete set of chemical states and some coarse-grained mechanical features. Their advantage is that they are more detailed than discrete kinetic models that treat the motor as one or two ''points'' that discretely hop along a track and yet allow full simulation of hand-over-hand stepping, in contrast to computationally expensive full atomistic models that also require large numbers of pa...

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confidence: 99%

Mechanochemical model for myosin V

Craig

Linke²

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…A completely rigid motor will have less diffusional space to explore and may bind more quickly than a completely flexible motor. But, previous modeling results have shown that a rigid motor is very sensitive to the binding site separation (determined by the structure of the dsDNA track), and thus it is also not clear a priori which optimal flexibility minimizes the diffusional search time [11].…”

Section: Introductionmentioning

confidence: 98%

“…Designing an artificial molecular motor using protein components may thus provide insight into subtle structurefunction aspects of biomolecular motors. We have proposed an artificial motor concept, the Tumbleweed (TW), which uses proteins as motor building blocks [11]. Proteins offer more diverse design choices than oligonucleotide structures because of the relatively large set of available amino acid building blocks that can produce large, three-dimensional structures.…”

Section: Introductionmentioning

confidence: 99%

“…1) [11]. Each repressor protein "foot" binds with high affinity to a unique double-stranded DNA (dsDNA) recognition sequence only when it has bound a specific ligand (a, b, and c, respectively) with a concentration in solution that can be controlled externally.…”

Section: Introductionmentioning

confidence: 99%

“…The Tumbleweed motor, thus, offers a unique opportunity to not only design a functioning motor, but also to actively tune the molecular design to optimize motor performance. The overall aim of this modeling study is to determine how motor [11]. Three repressor protein "feet" are attached by "ankle" joints to a hub made up of three rigid, coiled-coil "legs."…”

Section: Introductionmentioning

confidence: 99%

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Tuning the performance of an artificial protein motor

et al. 2011

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The Tumbleweed (TW) is a concept for an artificial, tri-pedal, protein-based motor designed to move unidirectionally along a linear track by a diffusive tumbling motion. Artificial motors offer the unique opportunity to explore how motor performance depends on design details in a way that is open to experimental investigation. Prior studies have shown that TW's ability to complete many successive steps can be critically dependent on the motor's diffusional step time. Here, we present a simulation study targeted at determining how to minimize the diffusional step time of the TW motor as a function of two particular design choices: nonspecific motor-track interactions and molecular flexibility. We determine an optimal nonspecific interaction strength and establish a set of criteria for optimal molecular flexibility as a function of the nonspecific interaction. We discuss our results in the context of similarities to biological, linear stepping diffusive molecular motors with the aim of identifying general engineering principles for protein motors.

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Hydrogels: From soft contact lenses and implants to self‐assembled nanomaterials

Kopeček

2009

J. Polym. Sci. A Polym. Chem.

373

235

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Hydrogels were the first biomaterials designed for clinical use. Their discovery and applications as soft contact lenses and implants are presented. This early hydrogel research served as a foundation for the expansion of biomedical polymers research into new directions: design of stimuli sensitive hydrogels that abruptly change their properties upon application of an external stimulus (pH, temperature, solvent, electrical field, biorecognition) and hydrogels as carriers for the delivery of drugs, peptides, and proteins. Finally, pathways to self-assembly of block and graft copolymers into hydrogels of precise 3D structures are introduced.

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The Tumbleweed: Towards a synthetic protein motor

Cited by 38 publications

References 82 publications

Mechanochemical model for myosin V

Mechanochemical model for myosin V

Tuning the performance of an artificial protein motor

Hydrogels: From soft contact lenses and implants to self‐assembled nanomaterials

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