| 1. |
- Boyle, Aimee L., et al.
(author)
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Squaring the Circle in Peptide Assembly: From Fibers to Discrete Nanostructures by de Novo Design
- 2012
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 134:37, s. 15457-15467
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Journal article (peer-reviewed)abstract
- The design of bioinspired nanostructures and materials of defined size and shape is challenging as it pushes our understanding of biomolecular assembly to its limits. In such endeavors, DNA is the current building block of choice because of its predictable and programmable self-assembly. The use of peptide- and protein-based systems, however, has potential advantages due to their more-varied chemistries, structures and functions, and the prospects for recombinant production through gene synthesis and expression. Here, we present the design and characterization of two complementary peptides programmed to form a parallel heterodimeric coiled coil, which we use as the building blocks for larger, supramolecular assemblies. To achieve the latter, the two peptides are joined via peptidic linkers of variable lengths to produce a range of assemblies, from flexible fibers of indefinite length, through large colloidal-scale assemblies, down to closed and discrete nanoscale objects of defined stoichiometry. We posit that the different modes of assembly reflect the interplay between steric constraints imposed by short linkers and the bulk of the helices, and entropic factors that favor the formation of many smaller objects as the linker length is increased. This approach, and the resulting linear and proteinogenic polypeptides, represents a new route for constructing complex peptide-based assemblies and biomaterials.
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| 2. |
- Kovacic, Suzana, et al.
(author)
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Construction and Characterization of Kilobasepair Densely Labeled Peptide-DNA
- 2014
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1526-4602 .- 1525-7797. ; 15:11, s. 4065-4072
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Journal article (peer-reviewed)abstract
- Directed assembly of biocompatible materials benefits from modular building blocks in which structural organization is independent of introduced functional modifications. For soft materials, such modifications have been limited. Here, long DNA is successfully functionalized with dense decoration by peptides. Following introduction of alkyne-modified nucleotides into kilobasepair DNA, measurements of persistence length show that DNA mechanics are unaltered by the dense incorporation of alkynes (similar to 1 alkyne/2 bp) and after click-chemistry attachment of a tunable density of peptides. Proteolytic cleavage of densely tethered peptides (similar to 1 peptide/3 bp) demonstrates addressability of the functional groups, showing that this accessible approach to creating hybrid structures can maintain orthogonality between backbone mechanics and overlaid function. The synthesis and characterization of these hybrid constructs establishes the groundwork for their implementation in future applications, such as building blocks in modular approaches to a range of problems in synthetic biology.
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| 3. |
- Kuwada, Nathan J., et al.
(author)
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Tuning the performance of an artificial protein motor
- 2011
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In: Physical Review E (Statistical, Nonlinear, and Soft Matter Physics). - 1539-3755. ; 84:3
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Journal article (peer-reviewed)abstract
- 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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| 4. |
- Samii, Laleh, et al.
(author)
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Time-dependent motor properties of multipedal molecular spiders
- 2011
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In: Physical Review E (Statistical, Nonlinear, and Soft Matter Physics). - 1539-3755. ; 84:3
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Journal article (peer-reviewed)abstract
- Molecular spiders are synthetic biomolecular walkers that use the asymmetry resulting from cleavage of their tracks to bias the direction of their stepping motion. Using Monte Carlo simulations that implement the Gillespie algorithm, we investigate the dependence of the biased motion of molecular spiders, along with binding time and processivity, on tunable experimental parameters, such as number of legs, span between the legs, and unbinding rate of a leg from a substrate site. We find that an increase in the number of legs increases the spiders' processivity and binding time but not their mean velocity. However, we can increase the mean velocity of spiders with simultaneous tuning of the span and the unbinding rate of a spider leg from a substrate site. To study the efficiency of molecular spiders, we introduce a time-dependent expression for the thermodynamic efficiency of a molecular motor, allowing us to account for the behavior of spider populations as a function of time. Based on this definition, we find that spiders exhibit transient motor function over time scales of many hours and have a maximum efficiency on the order of 1%, weak compared to other types of molecular motors.
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