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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<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, Apptest, RosettaFold and TrRosetta. the best model was obtained from AlphaFold2 ranking 6 out of 6 according to our QA parameters.
  
  
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<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 WWW with whole tau, paired helical filaments (PHF) of tau and (PHF*)
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We docked the WWW peptide with 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 style=" font-weight: bold; color: red; font-size:14px;"> ΔG = -173.217 </p>
  
 
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<p style=" font-weight: bold; color: red; font-size:14px;"> ΔG = -8.45 </p>
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<p style=" font-weight: bold; font-size:13px;"> ΔG = -8.45
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                       Figure 3.: Docked structure of WWW and PHF* of tau designed by Galaxy docking tool.
 
                       Figure 3.: Docked structure of WWW and PHF* of tau designed by Galaxy docking tool.
  
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<p style=" font-weight: bold; color: red; font-size:14px;"> ΔG = -8.255 </p>
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<p style=" font-weight: bold; font-size:13px;"> ΔG = -8.255
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Revision as of 15:44, 9 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, Apptest, 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.


Docking

We docked the WWW peptide with 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.


ΔG = -8.45 

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

ΔG = -8.255 

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


All of binding energies were calculated using prodigy tool.



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