3.1 Strategy for creating anti-EGFR scaffolds
Selecting an appropriate scaffold for grafting effective CDRs in binding
is crucial to mimic the antibody-receptor interaction. Accordingly, we
computationally designed small antibody mimetics with high affinity
against EGFR DIII based on the panitumumab antibody. Ideal traits of
scaffold candidates as CDRs acceptors include a suitable size (less than
180 amino acids) with a minimum of three variable loops, low disulfide
bonds, and non-immunogenicity. Then active CDRs in ligand-receptor
interaction were determined and immobilized randomly into variable loops
of each scaffold. All designed structures were analyzed (Table 1) and
after docking against EGFR DIII, the best ones from each scaffold were
selected for MD analysis. The Ramachandran plots of scFv and three
selected scaffolds are depicted in Fig.1, and the selected scaffolds’
residue information is shown in table 2.