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.