An epithelial sodium channel (ENaC)-specific aptamer determined through structure-based virtual screening for the development of hypertension early detection system

Abstract

Background: Epithelial sodium channel (ENaC) is a transmembrane protein involved in maintaining sodium levels in blood plasma. It is also a potential biomarker for the early detection of hypertension since the amount of ENaC is related to the familial history of hypertension. ENaC can be detected by an aptamer, a single-stranded DNA (ssDNA) or RNA which offers advantages over an antibody. This study aimed to obtain an ssDNA aptamer specific to ENaC through virtual screening. Methods: Forty-one aptamers were retrieved from the Protein Data Bank (PDB) and the RNA was converted to ssDNA aptamers. The X-ray crystallographic structure of ENaC protein was remodelled using Modeller 9.20 to resolve missing residues. Molecular docking of aptamers against ENaC was performed using Patchdock and Firedock, then the selected aptamer was subjected to molecular docking against other ion channel proteins to assess its selectivity to ENaC. A molecular dynamics (MD) simulation was also conducted using Amber16 to acquire an in-depth understanding of the interaction within the aptamer-ENaC complex. Results: The virtual screening suggested that the ssDNA of iSpinach aptamer (PDB: 5OB3) displayed the strongest binding to ENaC (-49.46 kcal/mol) and was selective for ENaC over the other ion protein channels. An MMGBSA calculation on the complex of aptamer-ENaC revealed binding energy of -42,12 kcal/mol. Conclusion: The iSpinach-based aptamer is a potential probe for detecting ENaC or iDE and may be useful for the development of hypertension early detection systems.