# Investigating the Structural and Functional Consequences of Pathogenic SNPs on Human VEGFA Dimer: Insights from Molecular Dynamics Study

## TL;DR

This study uses computational methods to explore how two harmful mutations affect the structure and function of the VEGFA protein dimer, which is important for blood vessel growth.

## Contribution

The study provides new structural insights into how pathogenic SNPs disrupt VEGFA dimer stability and receptor binding.

## Key findings

- Mutations R262Q and C266Y disrupt key interface interactions in VEGFA dimer.
- The mutations reduce dimer stability and alter receptor-binding shape.
- These structural changes may block normal signaling and biological functions.

## Abstract

Vascular endothelial
growth factor A (VEGFA) is a key
regulator
of angiogenesis. It forms a homodimer and binds to VEGF receptors
to activate signaling pathways important for blood vessel growth and
maintenance. In this study, we examined the structural and functional
effects of two deleterious mutants, R262Q and C266Y, using integrative
computational methods. Molecular dynamics simulations and principal
component analysis showed that both mutations disrupted crucial interface
interactions, including H-bonds, salt bridges, and disulfide linkages.
As a result, the dimer conformation became less stable, which was
also supported by binding free energy analysis. In addition, structural
superimposition analysis revealed that both mutations changed the
receptor-binding shape. This may block normal signaling and affect
biological functions. Overall, our findings provide structural insights
into how these mutations affect VEGFA dimer and may help guide the
development of new therapeutics.