Source 1review2018Current Opinion in Biotechnology
Toolkit/computational protein design
computational protein design
Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Computational protein design is an engineering methodology described in a 2018 review as a next-generation tool for expanding synthetic biology applications. The supplied evidence frames it as a design approach used alongside phage display and high-throughput binding assays rather than as a single molecular reagent.
Usefulness & Problems
Why this is useful
The available evidence indicates that computational protein design is useful for expanding the scope of synthetic biology applications. It appears in the context of a broader protein engineering workflow that can be combined with phage display and high-throughput binding assays.
Source:
We demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
Problem solved
The supplied review-level evidence suggests that this methodology addresses the need for next-generation tools to engineer proteins for synthetic biology. However, the specific design objectives, target classes, and quantitative performance problems solved are not provided in the evidence set.
Source:
We demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
Taxonomy & Function
Primary hierarchy
Technique Branch
Method: A concrete method used to build, optimize, or evolve an engineered system.
Mechanisms
small-molecule-responsive switchingTechniques
Computational DesignTarget processes
No target processes tagged yet.
Implementation Constraints
The supplied evidence only states that computational protein design can be used together with phage display and high-throughput binding assays. No specific software frameworks, structural inputs, host systems, construct architectures, or experimental implementation requirements are described here.
The evidence is sparse and largely review-level, with no direct quantitative benchmarks, case-by-case success rates, or mechanistic details for specific designed proteins. The included iLID application claim does not directly establish computational protein design as the causal method for that tool within the supplied evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Source 2primary paper2014Proceedings of the National Academy of Sciences
Ranked Claims
The review presents computational protein design as a next-generation tool to expand synthetic biology applications.
The review presents computational protein design as a next-generation tool to expand synthetic biology applications.
The review presents computational protein design as a next-generation tool to expand synthetic biology applications.
The review presents computational protein design as a next-generation tool to expand synthetic biology applications.
The review presents computational protein design as a next-generation tool to expand synthetic biology applications.
The review presents computational protein design as a next-generation tool to expand synthetic biology applications.
The review presents computational protein design as a next-generation tool to expand synthetic biology applications.
The switch was functionally demonstrated through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
We demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
The switch was functionally demonstrated through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
We demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
The switch was functionally demonstrated through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
We demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
The switch was functionally demonstrated through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
We demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
The switch was functionally demonstrated through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
We demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
The switch was functionally demonstrated through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
We demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
The switch was functionally demonstrated through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
We demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.
The switch was created by embedding the bacterial SsrA peptide in the C-terminal helix of the Avena sativa LOV2 domain.
To create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2 (LOV2) domain from Avena sativa.
The switch was created by embedding the bacterial SsrA peptide in the C-terminal helix of the Avena sativa LOV2 domain.
To create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2 (LOV2) domain from Avena sativa.
The switch was created by embedding the bacterial SsrA peptide in the C-terminal helix of the Avena sativa LOV2 domain.
To create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2 (LOV2) domain from Avena sativa.
The switch was created by embedding the bacterial SsrA peptide in the C-terminal helix of the Avena sativa LOV2 domain.
To create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2 (LOV2) domain from Avena sativa.
The switch was created by embedding the bacterial SsrA peptide in the C-terminal helix of the Avena sativa LOV2 domain.
To create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2 (LOV2) domain from Avena sativa.
The switch was created by embedding the bacterial SsrA peptide in the C-terminal helix of the Avena sativa LOV2 domain.
To create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2 (LOV2) domain from Avena sativa.
The switch was created by embedding the bacterial SsrA peptide in the C-terminal helix of the Avena sativa LOV2 domain.
To create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2 (LOV2) domain from Avena sativa.
In the dark, the SsrA peptide is sterically blocked from binding SspB, and blue-light activation allows binding by undocking the LOV2 C-terminal helix.
In the dark the SsrA peptide is sterically blocked from binding its natural binding partner, SspB. When activated with blue light, the C-terminal helix of the LOV2 domain undocks from the protein, allowing the SsrA peptide to bind SspB.
In the dark, the SsrA peptide is sterically blocked from binding SspB, and blue-light activation allows binding by undocking the LOV2 C-terminal helix.
In the dark the SsrA peptide is sterically blocked from binding its natural binding partner, SspB. When activated with blue light, the C-terminal helix of the LOV2 domain undocks from the protein, allowing the SsrA peptide to bind SspB.
In the dark, the SsrA peptide is sterically blocked from binding SspB, and blue-light activation allows binding by undocking the LOV2 C-terminal helix.
In the dark the SsrA peptide is sterically blocked from binding its natural binding partner, SspB. When activated with blue light, the C-terminal helix of the LOV2 domain undocks from the protein, allowing the SsrA peptide to bind SspB.
In the dark, the SsrA peptide is sterically blocked from binding SspB, and blue-light activation allows binding by undocking the LOV2 C-terminal helix.
In the dark the SsrA peptide is sterically blocked from binding its natural binding partner, SspB. When activated with blue light, the C-terminal helix of the LOV2 domain undocks from the protein, allowing the SsrA peptide to bind SspB.
In the dark, the SsrA peptide is sterically blocked from binding SspB, and blue-light activation allows binding by undocking the LOV2 C-terminal helix.
In the dark the SsrA peptide is sterically blocked from binding its natural binding partner, SspB. When activated with blue light, the C-terminal helix of the LOV2 domain undocks from the protein, allowing the SsrA peptide to bind SspB.
In the dark, the SsrA peptide is sterically blocked from binding SspB, and blue-light activation allows binding by undocking the LOV2 C-terminal helix.
In the dark the SsrA peptide is sterically blocked from binding its natural binding partner, SspB. When activated with blue light, the C-terminal helix of the LOV2 domain undocks from the protein, allowing the SsrA peptide to bind SspB.
In the dark, the SsrA peptide is sterically blocked from binding SspB, and blue-light activation allows binding by undocking the LOV2 C-terminal helix.
In the dark the SsrA peptide is sterically blocked from binding its natural binding partner, SspB. When activated with blue light, the C-terminal helix of the LOV2 domain undocks from the protein, allowing the SsrA peptide to bind SspB.
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
change in binding affinity for SspB with light stimulation twofold
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
change in binding affinity for SspB with light stimulation twofold
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
change in binding affinity for SspB with light stimulation twofold
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
change in binding affinity for SspB with light stimulation twofold
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
change in binding affinity for SspB with light stimulation twofold
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
change in binding affinity for SspB with light stimulation twofold
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
change in binding affinity for SspB with light stimulation twofold
The improved light inducible dimer iLID changes its affinity for SspB by over 50-fold with light stimulation.
create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation
change in affinity for SspB with light stimulation 50 fold
The improved light inducible dimer iLID changes its affinity for SspB by over 50-fold with light stimulation.
create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation
change in affinity for SspB with light stimulation 50 fold
The improved light inducible dimer iLID changes its affinity for SspB by over 50-fold with light stimulation.
create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation
change in affinity for SspB with light stimulation 50 fold
The improved light inducible dimer iLID changes its affinity for SspB by over 50-fold with light stimulation.
create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation
change in affinity for SspB with light stimulation 50 fold
The improved light inducible dimer iLID changes its affinity for SspB by over 50-fold with light stimulation.
create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation
change in affinity for SspB with light stimulation 50 fold
The improved light inducible dimer iLID changes its affinity for SspB by over 50-fold with light stimulation.
create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation
change in affinity for SspB with light stimulation 50 fold
The improved light inducible dimer iLID changes its affinity for SspB by over 50-fold with light stimulation.
create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation
change in affinity for SspB with light stimulation 50 fold
A crystal structure of iLID shows a critical interaction between the LOV2 surface and an engineered phenylalanine that more tightly pins the SsrA peptide against LOV2 in the dark.
A crystal structure of iLID shows a critical interaction between the surface of the LOV2 domain and a phenylalanine engineered to more tightly pin the SsrA peptide against the LOV2 domain in the dark.
A crystal structure of iLID shows a critical interaction between the LOV2 surface and an engineered phenylalanine that more tightly pins the SsrA peptide against LOV2 in the dark.
A crystal structure of iLID shows a critical interaction between the surface of the LOV2 domain and a phenylalanine engineered to more tightly pin the SsrA peptide against the LOV2 domain in the dark.
A crystal structure of iLID shows a critical interaction between the LOV2 surface and an engineered phenylalanine that more tightly pins the SsrA peptide against LOV2 in the dark.
A crystal structure of iLID shows a critical interaction between the surface of the LOV2 domain and a phenylalanine engineered to more tightly pin the SsrA peptide against the LOV2 domain in the dark.
A crystal structure of iLID shows a critical interaction between the LOV2 surface and an engineered phenylalanine that more tightly pins the SsrA peptide against LOV2 in the dark.
A crystal structure of iLID shows a critical interaction between the surface of the LOV2 domain and a phenylalanine engineered to more tightly pin the SsrA peptide against the LOV2 domain in the dark.
A crystal structure of iLID shows a critical interaction between the LOV2 surface and an engineered phenylalanine that more tightly pins the SsrA peptide against LOV2 in the dark.
A crystal structure of iLID shows a critical interaction between the surface of the LOV2 domain and a phenylalanine engineered to more tightly pin the SsrA peptide against the LOV2 domain in the dark.
A crystal structure of iLID shows a critical interaction between the LOV2 surface and an engineered phenylalanine that more tightly pins the SsrA peptide against LOV2 in the dark.
A crystal structure of iLID shows a critical interaction between the surface of the LOV2 domain and a phenylalanine engineered to more tightly pin the SsrA peptide against the LOV2 domain in the dark.
A crystal structure of iLID shows a critical interaction between the LOV2 surface and an engineered phenylalanine that more tightly pins the SsrA peptide against LOV2 in the dark.
A crystal structure of iLID shows a critical interaction between the surface of the LOV2 domain and a phenylalanine engineered to more tightly pin the SsrA peptide against the LOV2 domain in the dark.
Approval Evidence
2 sources1 linked approval claimfirst-pass slug computational-protein-design
Named directly in the review title: "Computational protein design — the next generation tool to expand synthetic biology applications".
Source:
we describe the use of computational protein design, phage display, and high-throughput binding assays
Source:
review scopesupports
The review presents computational protein design as a next-generation tool to expand synthetic biology applications.
Source:
Comparisons
Source-backed strengths
A cited review explicitly positions computational protein design as a next-generation tool for synthetic biology, supporting its relevance as a broadly enabling engineering strategy. The evidence also supports compatibility with complementary experimental selection and screening methods, specifically phage display and high-throughput binding assays.
Source:
To create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2 (LOV2) domain from Avena sativa.
Source:
Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation.
Source:
create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation
Ranked Citations
- 1.
- 2.