Part:BBa_K5271003
HER2-binding peptide -scrambled
A scrambled amino acid sequence that acts as a control for the HER2 binding region of the dual targeting nanobody -Panobody.
Profile
- Name: HER2-binding peptide -scrambled
- Base Pairs: 345 bp
- Amino acid: 115 a.a
- Origin: Synthetic
- Properties: A scrambled control for the dual targeting nanobody -Panobody.
Usage and Biology
The design of this basic part began with an in-house bioinformatics analysis. Based on the dry lab result, we chose EGFR and HER2 as the dual targets for our Biobrick design. We created a dual targeting nanobody -Panobody for EGFR and HER2. To verify our design, we used Alphafold to create a three-dimensional model of Panobody and its scrambled control, Panobody-scrambled. [Jumper et al., 2021] Subsequently, we perform a molecular docking analysis to examine the binding affinity of the scrambled control.
The molecular docking analysis of Panobody- scrambled revealed a less extensive and intricate binding network. The scrambled HER2 binding region of Panobody- scrambled interacts with significant residues of the HER2 receptor, such as Lys765, Thr759, and Ash838, forming key hydrogen bonds and salt bridges and π-π stacking interactions, with Tyr835 playing a stabilizing role (Fig. 1a). However, the overall interaction network was less comprehensive than that observed for the Panobody.
- Figure 1. (a) 3D and 2D visualizations of molecular docking between the HER2 binding region of Panobody -scrambled the HER2 receptor. (Ba) 3D and 2D visualizations of molecular docking between the EGFR binding region of Panobody -scrambled and the EGFR receptor.
Design Note
Our preliminary results when it is joined with the EGFR nanobody by a linker, the linker should avoid cysteine residues since it potentially reduces the solubility of the dual targeting nanobody in prokaryotic expression system.
Source
The sequence of the HER2-binding peptide -scrambled was randomly generated and had a same length with the HER2 binding region of Panobody.
Reference
- Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., ... & Hassabis, D. (2021). Highly accurate protein structure prediction with AlphaFold. nature, 596(7873), 583-589.
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]
//proteindomain/binding
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