Effect of Alternating Electric Field on the Conformation and Function of Interleukin-6

Interleukin-6 (IL-6) is a critical inflammatory factor, that plays an important role in the inflammatory process and immune system by binding with IL-6 receptor. Cold atmospheric plasma (CAP) has been proven to be efficient in lowering the expression of IL-6 in inflammatory reactions by experiments. However, it remains unclear whether the CAP-induced electric field will affect the protein conformation and function of IL-6. The molecular dynamics method is applied to reveal the electric field dependence of IL-6 in conformation change. We found that when the electric field frequency is higher than 30 MHz, the electric field period is too short to divert the total dipole moment, and can only change the unstable N terminal structure of IL-6. However, when the frequency is lower than 30 MHz, the polarization of IL-6 increases, resulting in the fracture of disulfide bonds between long helices and the reduction of IL-6 stability. As for another factor of electric field intensity, the conformation change of IL-6 becomes more and more drastic with the electric field intensity increasing, while the conformation changes little when the electric field intensity is lower than $0.5 \mathrm{~V} / \mathrm{nm}$. The final protein docking results showed that the CAPinduced electric field prevents some important docking residues of IL-6 and its receptor from binding under the conditions of 30 MHz frequency and $0.5 \mathrm{~V} / \mathrm{nm}$ intensity. This work suggests that the appropriate frequency and intensity of the electric field can affect the binding ability of IL-6 to its receptor to a certain extent, which can provide certain theoretical guidance for the parameter selection of CAP treatment related diseases.