Difference between revisions of "Part:BBa K4165007"

(Dry Lab)
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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
 
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
 
 
 
 
 
 
  
  

Revision as of 15:48, 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