Source 1primary paper2017FEBS Journal
Toolkit/molecular dynamics simulations
molecular dynamics simulations
Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Molecular dynamics simulations were used as a computational design method to guide construction of the PiL[D24] photoswitchable mPKM2-LOV2 fusion reported in the 2017 FEBS Journal study. In that context, the simulations supported engineering of a light-responsive pyruvate kinase chimera that preserved LOV2 photoreactivity and showed illumination-dependent changes in enzyme activity.
Usefulness & Problems
Why this is useful
This computational method was useful for informing design of a fusion between mammalian pyruvate kinase M2 and the LOV2 photosensory domain. The reported study links this design workflow to a construct with light-dependent biochemical and cellular effects, indicating value for engineering optically controlled allosteric proteins.
Problem solved
The method addressed the design problem of creating a functional light-responsive mPKM2-LOV2 chimera. Specifically, it was used to guide fusion design in a system where illumination altered pyruvate kinase kinetics and cellular pyruvate labeling from glucose.
Problem links
Molecular dynamics simulations are a plausible computational approach for modeling molecular behavior when crystallization is difficult. This aligns with the gap's need for computational guidance, but the provided summary only says it was used to guide design, not crystal growth.
Molecular dynamics simulations can generate candidate conformations and dynamic ensembles that may be compared against spectral observations. This could help narrow plausible structures when spectroscopy alone is underdetermined.
Molecular dynamics can support rational design of monomer interactions or assembly behavior, which may be useful in early-stage programmable polymer design. It is more relevant for design and screening than for synthesis itself.
Taxonomy & Function
Primary hierarchy
Technique Branch
Method: A concrete computational method used to design, rank, or analyze an engineered system.
Mechanisms
computational conformational modelingcomputational conformational modelinglight-induced allosteric switchinglight-induced allosteric switchingTechniques
Computational DesignTarget processes
No target processes tagged yet.
Input: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: builderswitch architecture: uncaging
The documented implementation context is design of the PiL[D24] mPKM2-LOV2 domain fusion described in the FEBS Journal 2017 study. The available evidence indicates a light-responsive construct containing LOV2 fused to mammalian PKM2, but it does not provide practical simulation setup details or software parameters.
The supplied evidence supports use of molecular dynamics simulations in a single reported design case, rather than as a broadly benchmarked platform. The evidence does not specify simulation protocols, force fields, predictive accuracy, computational cost, or independent replication across additional targets.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Light exposure causes secondary structure changes in PiL[D24] that are associated with a 30% decrease in Km for phosphoenolpyruvate and increased pyruvate kinase activity.
causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure
Km change for phosphoenolpyruvate 30 %
Light exposure causes secondary structure changes in PiL[D24] that are associated with a 30% decrease in Km for phosphoenolpyruvate and increased pyruvate kinase activity.
causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure
Km change for phosphoenolpyruvate 30 %
Light exposure causes secondary structure changes in PiL[D24] that are associated with a 30% decrease in Km for phosphoenolpyruvate and increased pyruvate kinase activity.
causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure
Km change for phosphoenolpyruvate 30 %
Light exposure causes secondary structure changes in PiL[D24] that are associated with a 30% decrease in Km for phosphoenolpyruvate and increased pyruvate kinase activity.
causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure
Km change for phosphoenolpyruvate 30 %
Light exposure causes secondary structure changes in PiL[D24] that are associated with a 30% decrease in Km for phosphoenolpyruvate and increased pyruvate kinase activity.
causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure
Km change for phosphoenolpyruvate 30 %
Light exposure causes secondary structure changes in PiL[D24] that are associated with a 30% decrease in Km for phosphoenolpyruvate and increased pyruvate kinase activity.
causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure
Km change for phosphoenolpyruvate 30 %
Light exposure causes secondary structure changes in PiL[D24] that are associated with a 30% decrease in Km for phosphoenolpyruvate and increased pyruvate kinase activity.
causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure
Km change for phosphoenolpyruvate 30 %
Light exposure causes secondary structure changes in PiL[D24] that are associated with a 30% decrease in Km for phosphoenolpyruvate and increased pyruvate kinase activity.
causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure
Km change for phosphoenolpyruvate 30 %
Light exposure causes secondary structure changes in PiL[D24] that are associated with a 30% decrease in Km for phosphoenolpyruvate and increased pyruvate kinase activity.
causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure
Km change for phosphoenolpyruvate 30 %
Light exposure causes secondary structure changes in PiL[D24] that are associated with a 30% decrease in Km for phosphoenolpyruvate and increased pyruvate kinase activity.
causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure
Km change for phosphoenolpyruvate 30 %
Expression of PiL[D24] in cells leads to a light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to a light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to a light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to a light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to a light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to a light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to a light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to a light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to a light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to a light-induced increase in labelling of pyruvate from glucose.
Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose.
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
The LOV2 photoreaction is preserved in the PiL[D24] chimera.
The LOV2 photoreaction is preserved in the PiL[D24] chimera
The LOV2 photoreaction is preserved in the PiL[D24] chimera.
The LOV2 photoreaction is preserved in the PiL[D24] chimera
The LOV2 photoreaction is preserved in the PiL[D24] chimera.
The LOV2 photoreaction is preserved in the PiL[D24] chimera
The LOV2 photoreaction is preserved in the PiL[D24] chimera.
The LOV2 photoreaction is preserved in the PiL[D24] chimera
The LOV2 photoreaction is preserved in the PiL[D24] chimera.
The LOV2 photoreaction is preserved in the PiL[D24] chimera
The LOV2 photoreaction is preserved in the PiL[D24] chimera.
The LOV2 photoreaction is preserved in the PiL[D24] chimera
The LOV2 photoreaction is preserved in the PiL[D24] chimera.
The LOV2 photoreaction is preserved in the PiL[D24] chimera
The LOV2 photoreaction is preserved in the PiL[D24] chimera.
The LOV2 photoreaction is preserved in the PiL[D24] chimera
The LOV2 photoreaction is preserved in the PiL[D24] chimera.
The LOV2 photoreaction is preserved in the PiL[D24] chimera
The LOV2 photoreaction is preserved in the PiL[D24] chimera.
The LOV2 photoreaction is preserved in the PiL[D24] chimera
PiL[D24] could provide a means to modulate cellular glucose metabolism remotely.
PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner
PiL[D24] could provide a means to modulate cellular glucose metabolism remotely.
PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner
PiL[D24] could provide a means to modulate cellular glucose metabolism remotely.
PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner
PiL[D24] could provide a means to modulate cellular glucose metabolism remotely.
PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner
PiL[D24] could provide a means to modulate cellular glucose metabolism remotely.
PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner
PiL[D24] could provide a means to modulate cellular glucose metabolism remotely.
PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner
PiL[D24] could provide a means to modulate cellular glucose metabolism remotely.
PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner
PiL[D24] could provide a means to modulate cellular glucose metabolism remotely.
PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner
PiL[D24] could provide a means to modulate cellular glucose metabolism remotely.
PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner
PiL[D24] could provide a means to modulate cellular glucose metabolism remotely.
PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner
The light-induced change in PiL[D24] activity is reversible upon light withdrawal.
Importantly, this change in activity is reversible upon light withdrawal.
The light-induced change in PiL[D24] activity is reversible upon light withdrawal.
Importantly, this change in activity is reversible upon light withdrawal.
The light-induced change in PiL[D24] activity is reversible upon light withdrawal.
Importantly, this change in activity is reversible upon light withdrawal.
The light-induced change in PiL[D24] activity is reversible upon light withdrawal.
Importantly, this change in activity is reversible upon light withdrawal.
The light-induced change in PiL[D24] activity is reversible upon light withdrawal.
Importantly, this change in activity is reversible upon light withdrawal.
The light-induced change in PiL[D24] activity is reversible upon light withdrawal.
Importantly, this change in activity is reversible upon light withdrawal.
The light-induced change in PiL[D24] activity is reversible upon light withdrawal.
Importantly, this change in activity is reversible upon light withdrawal.
The light-induced change in PiL[D24] activity is reversible upon light withdrawal.
Importantly, this change in activity is reversible upon light withdrawal.
The light-induced change in PiL[D24] activity is reversible upon light withdrawal.
Importantly, this change in activity is reversible upon light withdrawal.
The light-induced change in PiL[D24] activity is reversible upon light withdrawal.
Importantly, this change in activity is reversible upon light withdrawal.
Approval Evidence
5 sources10 linked approval claimsfirst-pass slug molecular-dynamics-simulations
molecular dynamics (MD) simulations augment AlphaFold's static models by sampling conformational flexibility and testing stability.
Source:
this work characterizes early lipid-driven dimerization using molecular dynamics simulations
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computational approaches-particularly Molecular Dynamics (MD) simulations and Artificial Intelligence (AI)-have emerged as transformative tools to accelerate nanocarrier design and optimise their properties
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we have used molecular dynamics simulations to guide the design
Source:
as we demonstrate using molecular dynamics simulations
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capabilitysupports
Molecular dynamics simulations augment AlphaFold static models by sampling conformational flexibility and testing stability.
molecular dynamics (MD) simulations augment AlphaFold's static models by sampling conformational flexibility and testing stability
Source:
capabilitysupports
Molecular Dynamics simulations and Artificial Intelligence are described as transformative computational approaches for accelerating nanocarrier design and optimizing nanocarrier properties.
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design impactsupports
Computational approaches can be used to refine nanoparticle composition to improve biocompatibility, reduce toxicity, and achieve more precise drug targeting.
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limitationsupports
Data scarcity and complex in vivo dynamics are identified as key challenges for integrating computational insights into next generation nanodelivery systems.
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mechanistic insightsupports
Compared with aqueous solution, a lipid membrane model reveals that protein-lipid interactions critically guide inter-protein residue alignment and binding during p7 dimer interactions.
Comparing dimer interactions in aqueous solution versus on a lipid membrane model reveal that protein-lipid interactions critically guide inter-protein residue alignment and binding.
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mechanistic insightsupports
Hydrophobic contacts and hydrogen bonding between key residues and phosphatidylcholine/phosphatidylinositol lipids drive helix interactions that promote p7 oligomerization, particularly involving the first helix.
Hydrophobic contacts and hydrogen bonding between key residues and phosphatidylcholine/phosphatidylinositol lipids drive essential helix interactions that promote p7 oligomerization, particularly involving the first helix.
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mechanistic insightsupports
MD simulations provide atomic-to-mesoscale insight into nanoparticle interactions with biological membranes, including how surface charge density, ligand functionalisation, and nanoparticle size affect cellular uptake and stability.
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mechanistic insightsupports
Molecular dynamics simulations characterize early lipid-driven dimerization of hepatitis C virus p7.
Using the hepatitis C virus p7 hexamer as a representative of proteins with complex transmembrane topology, this work characterizes early lipid-driven dimerization using molecular dynamics simulations.
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workflow rolesupports
In silico models are described as guiding experimental validation, informing rational design strategies, and streamlining translation of nanodelivery systems from bench to bedside.
Source:
engineered designsupports
Molecular dynamics simulations were used to guide the design of the PiL[D24] mPKM2-LOV2 fusion.
we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24])
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Comparisons
Source-backed strengths
The main demonstrated strength is that molecular dynamics simulations were explicitly used to guide design of a successful photoswitchable enzyme construct. In the resulting PiL[D24] tool, light exposure was associated with secondary-structure changes, a 30% decrease in Km for phosphoenolpyruvate, increased pyruvate kinase activity, and increased labeling of pyruvate from glucose in cells.
Compared with AQTrip EL222 variant
molecular dynamics simulations and AQTrip EL222 variant address a similar problem space.
Shared frame: shared mechanisms: light-induced allosteric switching; same primary input modality: light
Strengths here: appears more independently replicated; looks easier to implement in practice.
Compared with Markov State Modeling
molecular dynamics simulations and Markov State Modeling address a similar problem space.
Shared frame: same top-level item type; shared mechanisms: light-induced allosteric switching; same primary input modality: light
Strengths here: appears more independently replicated; looks easier to implement in practice.
Compared with model bioinformatics analysis
molecular dynamics simulations and model bioinformatics analysis address a similar problem space.
Shared frame: same top-level item type; same primary input modality: light
Strengths here: appears more independently replicated; looks easier to implement in practice.
Ranked Citations
- 1.