Difference between revisions of "Part:BBa K4165006"

Revision as of 10:53, 5 October 2022

TD28rev (Tau binding peptide)

A synthetic peptide that is used for targeting misfolded tau protein (BBa_K4165009) as it binds to PHF6 of tau fibrils.

Usage and Biology

A short synthetic peptide acquired by mirror image phage display for binding to tau fibrils at its seed sequence ‘VQIVYK’ called the PHF6. The aggregation of microtubule-associated tau protein starts at this seed to form neurofibrillary tangles inside the brain, which are the main cause of Alzheimer’s disease (AD). Accordingly, this peptide would be suitable to act as our targeting domain for the aggregations.

Dry Lab characterization

Modeling

We modeled the peptide with (Alphafold2, Apptest, iTASSER, and TRrosetta) and our top model was obtained from Apptest scoring 6 out of 6 according to our quality assessment code.

                                   Figure 1.: Predicted 3D structure of TD28REV peptide.

Docking

Docking was performed using three different algorithms (Lightdock, Cluspro, and Galaxy web server) to test the interaction and binding affinity of TD28REV to both tau PHF filament and amyloid beta aggregates, this was followed by ranking of docked models and selection of models with the lowest free energy of binding.

TD28REV vs Tau seed (PHF):

ΔG = -170.825

                                  Figure 2.: Visualization of TD28REV docked with Tau PHF.

TD28REV vs Amyloid beta:

ΔG = -40.34

                                  Figure 3.: Visualization of TD28REV docked with Amyloid beta.

References

Dammers, C., Yolcu, D., Kukuk, L., Willbold, D., Pickhardt, M., Mandelkow, E., ... & Funke, S. A. (2016). Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease. PLoS One, 11(12), e0167432.