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.