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

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.