5. Conclusion
This study aims to identify novel antibody mimetics scaffolds against the EGFR DIII whose binding sites overlap with EGF. Herein, molecular docking and MD simulation were successfully performed to design novel binders to EGFR DIII based on the CDR grafting technique. A set of 36 binders designed by loop randomization was screened by the molecular docking method. Eventually, the relative stability of the three selected scaffolds was validated by MD analysis. The scFv structure of panitumumab was designed to be compared with other designed binders. Trajectories analysis showed that all four complexes were structurally stable during the 50 ns MD run. From this study, two Scaf1 and Scaf2 showed promising high affinity against EGFR in comparison to 5SX4 and scFv complexes. Thus, the results of this study indicate that the anti-EGFR activity of these compounds could pose a great deal of significance against highly overexpressed EGFR cancers. These detailed analyses indicate that the computational antibody mimetics approach through the CDR grafting technique is very efficient. This in silico study may offer the opportunity to explore these scaffolds in vitro against EGFR.