Dina Ratna Komala
1* 
, Ari Hardianto
1 , Shabarni Gaffar
1 , Yeni Wahyuni Hartati
1 1 Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Indonesia.
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.