Computation‐Guided Design of a Stimulus‐Responsive Multienzyme Supramolecular Assembly

Yang, Lu; Dolan, Elliott M.; Tan, Sophia K.; Lin, Tianyun; Sontag, Eduardo D.; Khare, Sagar D.

doi:10.1002/cbic.201700425

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…1B,C,D). We have previously utilized a similar binding domain-peptide fusion strategy to design non-propagating multi-component enzyme complexes 50 .…”

Section: Main Textmentioning

confidence: 99%

Stimulus-responsive Self-Assembly of Protein-Based Fractals by Computational Design

Hernandez

Hansen

Zhu

et al. 2018

Preprint

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23 †Contributed equally to this work 24 Main Text: 1 Fractional-dimensional (fractal) geometrya property of shapes that are invariant or nearly 2 invariant to scale magnification or contraction across many length scalesis a common feature of 3 many natural objects 1,2 . Fractal forms are ubiquitous in geology, e.g., in the architecture of 4 mountain ranges, coastlines, snowflakes, and in physiology, e.g., neuronal and capillary networks, 5 and nasal membranes, where highly efficient molecular exchange occurs due to a fractal-induced 6 high surface area:volume ratio 3 . Fabrication of fractal-like nanomaterials affords high physical 7 connectivity within patterned objects 4 , ultrasensitive detection of target binding moieties by 8

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“…1B,C,D). We have previously utilized a similar binding domain-peptide fusion strategy to design non-propagating multi-component enzyme complexes 50 .…”

Section: Main Textmentioning

confidence: 99%

Stimulus-responsive Self-Assembly of Protein-Based Fractals by Computational Design

Hernandez

Hansen

Zhu

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…1B,C,D). We have previously utilized a similar binding domain-peptide fusion strategy to design non-propagating multicomponent enzyme complexes 50 .…”

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confidence: 99%

Stimulus-responsive self-assembly of protein-based fractals by computational design

et al. 2019

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Fractal topologies, which are statistically self-similar over multiple length scales, are pervasive in nature. The recurrence of patterns at increasing length scales in fractal-shaped branched objects, e.g., trees, lungs, and sponges, results in high effective surface areas, and provides key functional advantages, e.g., for molecular trapping and exchange. Mimicking these topologies in designed protein-based assemblies will provide access to novel classes of functional biomaterials for wide ranging applications. Here we describe a computational design approach for the reversible self-assembly of proteins into tunable supramolecular fractal-like topologies in response to phosphorylation. Computationally-guided atomic-resolution modeling of fusions of symmetric, oligomeric proteins with Src homology 2 (SH2) binding domain and its phosphorylatable ligand peptide was used to design iterative branching leading to assembly formation by two enzymes of the atrazine degradation pathway. Structural characterization using various microscopy techniques and Cryo-electron tomography revealed a variety of dendritic, hyperbranched, and sponge-like topologies which are self-similar over three decades (~10nm-10m) of length scale, in agreement with models from multi-scale computational simulations.Control over assembly topology and formation dynamics is demonstrated. Owing to their sponge-like structure on the nanoscale, fractal assemblies are capable of efficient and phosphorylation-dependent reversible macromolecular capture. The described design framework should enable the construction of a variety of novel, spatiotemporally responsive biomaterials featuring fractal topologies.

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“…3C ). This kind of information is key in designing optimally productive biosynthetic processes, and might call for a dynamic organizational transition as culture conditions change, or simply for the choice of an organizational strategy that is robust to the perturbations in question 72 .…”

Section: Resultsmentioning

confidence: 99%

Spatially organizing biochemistry: choosing a strategy to translate synthetic biology to the factory

Jakobson

Tullman‐Ercek

Mangan

2018

Sci Rep

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Natural biochemical systems are ubiquitously organized both in space and time. Engineering the spatial organization of biochemistry has emerged as a key theme of synthetic biology, with numerous technologies promising improved biosynthetic pathway performance. One strategy, however, may produce disparate results for different biosynthetic pathways. We use a spatially resolved kinetic model to explore this fundamental design choice in systems and synthetic biology. We predict that two example biosynthetic pathways have distinct optimal organization strategies that vary based on pathway-dependent and cell-extrinsic factors. Moreover, we demonstrate that the optimal design varies as a function of kinetic and biophysical properties, as well as culture conditions. Our results suggest that organizing biosynthesis has the potential to substantially improve performance, but that choosing the appropriate strategy is key. The flexible design-space analysis we propose can be adapted to diverse biosynthetic pathways, and lays a foundation to rationally choose organization strategies for biosynthesis.

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Computation‐Guided Design of a Stimulus‐Responsive Multienzyme Supramolecular Assembly

Cited by 9 publications

References 37 publications

Stimulus-responsive Self-Assembly of Protein-Based Fractals by Computational Design

Stimulus-responsive Self-Assembly of Protein-Based Fractals by Computational Design

Stimulus-responsive self-assembly of protein-based fractals by computational design

Spatially organizing biochemistry: choosing a strategy to translate synthetic biology to the factory

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