Abstract
Background: EphrinB2 ligand and its associated receptor have been responsible for mediating signal transduction pathways related to developmental, cell segmentation processes, cell proliferation, etc. Aberrations in ephb2 gene result in altered EPHB2 receptor protein, which in turn, affect the related biological processes.
Objective: The objective of this study is to determine the most lethal, non-synonymous SNPs associated with ephb2 gene and administer the effects of the mutation in the ligand-binding domain of EPHB2 protein. Understanding the molecular consequences of the detrimental SNPs and the mechanism, via which it deters the biological functions of the protein, will aid in predicting its impact on biological pathways.
Methods: We shortlisted the non-synonymous single nucleotide variants and observed the impact on phenotypic properties based on molecular dynamics simulations.
Results: Results suggest the introduction of detrimental nsSNP causes reduction in its stability, binding affinity for the associated ligand, namely Ephrin, and increases the enthalpy of the entire system.
Conclusion: These observations further enhance our understanding at the molecular level about the effects of genomic variants occurring in populations, and the mechanism by which, it leads to changes in susceptibility towards certain disease symptoms on the individual basis.