Antioxidative Properties of Usnic Acid and Its Interaction with Tyrosyl-DNA Phosphodiesterase

In this study are investigated antioxidative properties of usnic acid, as well as its interaction with tyrosyl-DNA phosphodiesterase 1 (TDP1). Antioxidative properties are estimated on the basis of the Density Functional Theory (DFT) calculations. For this propose, full optimization of parent molecule of usnic acid and corresponding radical cation, radicals and anions are done at M05-2X/6-311++G(d,p) level of theory. The CPCM solvation model was applied to approximate the influence of polar and non-polar solvent. Obtained results indicate single electron transfer followed by the proton transfer as thermodynamically the most unfavorable mechanism of antioxidant action. The lowest values are achieved for proton affinity, and that pointed out sequential proton loss electron transfer mechanism as dominant antioxidative mechanism. The second part of this study is the examination of the interaction between usnic acid and TDP1, which is an enzyme responsible for repairing the protein-DNA bond in the cells. In order to perform molecular docking simulation AutoDock 4.0 software is used. Analysis of obtained data specifies interactions with Asn162, Leu168, Gly182, Tyr167 and Ser485 as the most significant. Further, the molecular dynamic simulation is performed using NAMD software. It is noticed that similar interactions are obtained.