In-silico study of single-strand DNA aptamers against cortisol as a potential biomarker receptor in therapeutics and diagnostics

Abstract

Stress hormone is the number one adversary to the general health in human all over the world. In the presence of stress, cortisol, a glucocorticoid hormone synthesized by the stimulation of adrenal cortex will be secreted. Cortisol has immunosuppressive and anti-inflammatory effects, increases heart rate and blood pressure, and represses growth, and digestive and reproductive activities. Aptamers are synthetically derived nucleic acids has been long studied as a substitute of antibodies for therapeutics and diagnostics purposes. Current study focuses on in-silico approach of molecular docking and molecular dynamics simulation to study the interactions between single-strand DNA aptamers and cortisol in comparisons with the glucocorticoid receptor. In silico study were known to solve a plethora of biological related target study including the latest on COVID19 polymerase which is the inhibitors target protein. In current study, the tertiary conformational structures of ten single-strand DNA aptamers which experimentally derived were designed and docked against cortisol and compared with the binding of glucocorticoid receptor (PDB:4P6X). Binding affinity, number of hydrogen bonds and hydrophobic interactions were analyzed. The aptamer-cortisol complex with the lowest binding energy value was selected for 50 ns (ns) molecular dynamics simulation. Docking result shows that although number of intra-molecular hydrogen bond formed affecting the binding energy value of aptamer-cortisol complexes, hydrophobic interaction surrounding the cortisol is more important in determining the affinity of cortisol towards its receptor. Aptamer-1 shows the lowest binding energy value formed against cortisol (-10.1 kcal/mol) in comparison with other aptamers. Molecular dynamics simulation of Aptamer-1-cortisol complex shows that RMSD of glucocorticoid receptor-cortisol is lower in comparison with Aptamer 1-cortisol, with higher number of intra-molecular hydrogen bonds. Although the stability of receptor-cortisol is higher compared to Aptamer-1 complex, MMPBSA value of the last 10 ns of MD simulation prove that Aptamer-1-cortisol complex has the stability up to 50 ns of simulation. Further study to improve the single strand DNA aptamer binding against cortisol should be considered.