Binding studies of sertraline hydrochloride with CT-DNA using experimental and computational techniques.

Sertraline Hydrochloride (STH) is an antidepressant drug that belongs to the selective serotonin reuptake inhibitor family (SSRIs), which inhibits serotonin uptake in presynaptic nerve fibers. The use of these medications without a legitimate prescription might result in adverse effects, and in rare circumstances, death. The interaction mechanism and binding mode of STH with duplex DNA were extensively investigated using spectroscopic and modeling techniques at different temperatures. The hypochromic shift of the absorption spectra of STH on binding with CT-DNA indicated groove binding. Fluorescence spectroscopic studies showed that CT-DNA quenches the fluorescence intensity of STH through a static quenching mechanism. The thermodynamic parameters indicated that the complex formation was spontaneous, and enthalpy driven. The competitive displacement binding study revealed that STH displaced DAPI from the minor groove of DNA. Molecular docking and molecular dynamics simulations also revealed that the complex was stable over 150 ns and that STH preferred the minor groove of DNA. The binding energy of the stable conformations were evaluated through MM/PBSA methods. A comparison of the bound poses at different timescales showed minor changes in STH structure upon DNA binding. Furthermore, a structural analysis of CT-DNA indicated that STH induced changes in the sugar-phosphate backbone had an impact on the minor groove's width which are in agreement with the CD spectroscopic results. This study provides a better understanding of STH binding with duplex DNA.