Difference between revisions of "Part:BBa K4165007"
 
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<partinfo>BBa_K4165007 short</partinfo>
 
<partinfo>BBa_K4165007 short</partinfo>
  
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Synthetic peptide used to bind to the aggregations of misfolded tau protein (BBa_K4165009) and toxic Amyloid beta plaques (BBa_).
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Synthetic peptide used to bind to the aggregations of misfolded tau protein (BBa_K4165009) and toxic Amyloid beta plaques (BBa_K4165005).
  
  
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===Usage and Biology===
 
===Usage and Biology===
  
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WWW peptide is designed to inhibit the fibrilization of tau which is one of the main drivers of Alzheimer’s disease and other dementia diseases. PHF* (VQIINK) is the site that derives tau aggregation. WWW can bind to PHF* in a means that can disrupt the interface between each PHF* and consequently reduce the aggregates. Accordingly, this peptide would be suitable to act as the targeting domain in our systems.
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WWW peptide is designed to inhibit the fibrilization of tau which is one of the main drivers of Alzheimer’s disease and other types of dementia. PHF* (VQIINK) is the site that derives the aggregation, WWW can bind to PHF* in a means that can disrupt the interaction between the filaments and consequently reduce the aggregates. Accordingly, this peptide would be suitable to act as the targeting domain in our systems.
  
  
 
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<span class='h3bb'>Sequence and Features</span>
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===<span class='h3bb'>Sequence and Features</span>===
 
<partinfo>BBa_K4165007 SequenceAndFeatures</partinfo>
 
<partinfo>BBa_K4165007 SequenceAndFeatures</partinfo>
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<p style=" font-weight: bold; font-size:14px;"> Modeling </p>
 
<p style=" font-weight: bold; font-size:14px;"> Modeling </p>
  
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WWW peptide has been designed using AlphaFold2, Apptest, RosettaFold and TRrosetta. the best model obtained from AlphaFold2 with parameters values: cbeta_deviations 0, clashscore 0, molprobity 1.26, ramachandran_favored 100, ramachandran_outliers 0,Qmean4 -2.60904, and Qmean6 -1.56177
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WWW peptide was modeled using AlphaFold2, App test, RosettaFold, and TrRosetta. the best model was obtained from AlphaFold2 ranking 6 out of 6 according to our QA parameters.
  
  
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</html>
 
</html>
  
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                            Figure 1.: Predicted 3D structure of Synthetic peptide WWW.
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                          Figure 1.: Predicted 3D structure of Synthetic peptide WWW visualized by Pymol.
  
  
 
<p style=" font-weight: bold; font-size:14px;"> Docking </p>
 
<p style=" font-weight: bold; font-size:14px;"> Docking </p>
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We docked the WWW peptide with the whole tau, paired helical filaments of tau (PHF) and (PHF*)
  
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<p style=" font-weight: bold; font-size:13px;"> ΔG = -173.217
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</p>
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<p style=" font-weight: bold; color: red; font-size:14px;"> ΔG = -173.217 </p>
  
 
<html>
 
<html>
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</html>
 
</html>
  
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                            Figure 2.: Docked structure of WWW and whole tau.
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              Figure 2.: Docked structure of WWW and whole tau designed by Galaxy docking tool visualized by Pymol.
  
  
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<p style=" font-weight: bold; color: red; font-size:14px;"> ΔG = -8.45 </p>
  
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===References===
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<html>
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/wwwphfast.png" style="margin-left:200px;" alt="" width="500" /></p>
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</html>
  
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1. Goedert, M., & Spillantini, M. G. (2017). Propagation of Tau aggregates. Molecular Brain, 10. https://doi.org/10.1186/s13041-017-0298-7
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              Figure 3.: Docked structure of WWW and PHF* of tau designed by Galaxy docking tool visualized by Pymol.
  
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2. Etienne, M. A., Edwin, N. J., Aucoin, J. P., Russo, P. S., McCarley, R. L., & Hammer, R. P. (2007). Beta-amyloid protein aggregation. Methods in molecular biology (Clifton, N.J.), 386, 203–225. https://doi.org/10.1007/1-59745-430-3_7
 
  
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3. Seidler, P., Boyer, D., Rodriguez, J., Sawaya, M., Cascio, D., Murray, K., Gonen, T., & Eisenberg, D. (2018). Structure-based inhibitors of tau aggregation. Nature chemistry, 10(2), 170. https://doi.org/10.1038/nchem.2889
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<p style=" font-weight: bold; color: red; font-size:14px;"> ΔG = -8.255 </p>
  
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<html>
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/www-phf.png" style="margin-left:200px;" alt="" width="500" /></p>
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</html>
  
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            Figure 4.: Docked structure of WWW and PHF of tau designed by Galaxy docking tool visualized by Pymol.
  
  
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<p style=" font-weight: bold; font-size:13px;"> All of binding energies were calculated using prodigy tool.
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</p>
  
  
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<p style=" font-weight: bold; font-size:14px;"> Mathematical modeling </p>
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<p style=" font-weight: bold; font-size:14px;">Transcription rate and translation rate under T7 promotor </p>
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the mathematical modeling was based on our code for the calculation of transcription and translation (you can find it in the code section) beside with the estimated results from the wet lab.
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 +
<html>
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<p><img src="https://static.igem.wiki/teams/4165/wiki/dry-lab/mathematical-modeling/mathematical-modeling/www2.png" style="margin-left:200px;" alt="" width="500" /></p>
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</html>
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              Figure 5.: this figure shows the results from the transcription and translation code showing the
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                    variation of mRNA and protein concentrations with time compared with the wet lab results.
 +
 +
===References===
 +
 +
1. Goedert, M., & Spillantini, M. G. (2017). Propagation of Tau aggregates. Molecular Brain, 10. https://doi.org/10.1186/s13041-017-0298-7
 +
 +
2. Etienne, M. A., Edwin, N. J., Aucoin, J. P., Russo, P. S., McCarley, R. L., & Hammer, R. P. (2007). Beta-amyloid protein aggregation. Methods in molecular biology (Clifton, N.J.), 386, 203–225. https://doi.org/10.1007/1-59745-430-3_7
 +
 +
3. Seidler, P., Boyer, D., Rodriguez, J., Sawaya, M., Cascio, D., Murray, K., Gonen, T., & Eisenberg, D. (2018). Structure-based inhibitors of tau aggregation. Nature chemistry, 10(2), 170. https://doi.org/10.1038/nchem.2889
  
  

Latest revision as of 05:32, 11 October 2022


WWW (Tau binding peptide)

Synthetic peptide used to bind to the aggregations of misfolded tau protein (BBa_K4165009) and toxic Amyloid beta plaques (BBa_K4165005).


Usage and Biology

WWW peptide is designed to inhibit the fibrilization of tau which is one of the main drivers of Alzheimer’s disease and other types of dementia. PHF* (VQIINK) is the site that derives the aggregation, WWW can bind to PHF* in a means that can disrupt the interaction between the filaments and consequently reduce the aggregates. Accordingly, this peptide would be suitable to act as the targeting domain in our systems.


Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    COMPATIBLE WITH RFC[21]
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE WITH RFC[1000]


Dry Lab

Modeling

WWW peptide was modeled using AlphaFold2, App test, RosettaFold, and TrRosetta. the best model was obtained from AlphaFold2 ranking 6 out of 6 according to our QA parameters. 


                          Figure 1.: Predicted 3D structure of Synthetic peptide WWW visualized by Pymol.


Docking

We docked the WWW peptide with the whole tau, paired helical filaments of tau (PHF) and (PHF*)


ΔG = -173.217 

             Figure 2.: Docked structure of WWW and whole tau designed by Galaxy docking tool visualized by Pymol.


ΔG = -8.45 

             Figure 3.: Docked structure of WWW and PHF* of tau designed by Galaxy docking tool visualized by Pymol.


ΔG = -8.255 

            Figure 4.: Docked structure of WWW and PHF of tau designed by Galaxy docking tool visualized by Pymol.


All of binding energies were calculated using prodigy tool.


Mathematical modeling

Transcription rate and translation rate under T7 promotor

the mathematical modeling was based on our code for the calculation of transcription and translation (you can find it in the code section) beside with the estimated results from the wet lab. 


              Figure 5.: this figure shows the results from the transcription and translation code showing the 
                   variation of mRNA and protein concentrations with time compared with the wet lab results.

References

1. Goedert, M., & Spillantini, M. G. (2017). Propagation of Tau aggregates. Molecular Brain, 10. https://doi.org/10.1186/s13041-017-0298-7

2. Etienne, M. A., Edwin, N. J., Aucoin, J. P., Russo, P. S., McCarley, R. L., & Hammer, R. P. (2007). Beta-amyloid protein aggregation. Methods in molecular biology (Clifton, N.J.), 386, 203–225. https://doi.org/10.1007/1-59745-430-3_7

3. Seidler, P., Boyer, D., Rodriguez, J., Sawaya, M., Cascio, D., Murray, K., Gonen, T., & Eisenberg, D. (2018). Structure-based inhibitors of tau aggregation. Nature chemistry, 10(2), 170. https://doi.org/10.1038/nchem.2889