# In Silico Design and Analysis of a Novel Ranibizumab-derived Peptide against the Vascular Endothelial Growth Factor

## TL;DR

Researchers designed a new anti-VEGF peptide based on ranibizumab to potentially treat neovascular age-related macular degeneration by inhibiting VEGF/VEGFR2 interaction.

## Contribution

A novel ranibizumab-derived peptide was designed and validated in silico for improved anti-VEGF binding affinity.

## Key findings

- Effective amino acids in VEGF-ranibizumab interaction were identified using molecular modeling tools.
- Random mutagenesis and MD simulations revealed a peptide with high binding affinity and stability.
- Grafting into frameworks like kB1 and MCoTI-II enhanced peptide-VEGF binding affinity.

## Abstract

Blocking the interaction between vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR2) is recognized as an effective strategy for treating neovascular age-related macular degeneration (nAMD). The present research aimed at designing and modelling an anti-VEGF peptide based on ranibizumab for potential application in inhibiting the VEGF/VEGFR2 interaction.

Effective amino acids in the interaction between VEGF and ranibizumab were analyzed using Swiss-PdbViewer (SPDBV), PyMOL, and Chimera software. The effective area in this interaction was determined and applied as a basis to design a peptide. Then, this sequence (containing 25 amino acids) was subjected to random mutagenesis, and the binding affinity of the resulting peptides was analyzed using the ClusPro software. Subsequently, GROMACS v5.0.6 was employed for molecular dynamics (MD) simulations to evaluate the stability of target-ligand complexes. Ultimately, the peptide exhibiting the highest affinity was grafted into the kB1 and MCoTI-II frameworks to enhance the stability.

This modification resulted in improved peptide-VEGF binding affinity, demonstrating the potential of in silico design for creating effective anti-angiogenic peptides in antiangiogenic therapies.

The findings from this study provide a basis for designing and validating peptide inhibitors against VEGF.