Electric Field Effect on Protein Dissociation: a Computational Evaluation of the Energy Barrier over Thiol-Disulfide Interchange Reaction in TRX-TXNIP Complex as an Interaction Model for Biological Antioxidant Response

Cells are susceptible of oxidative stress and have intracellular signaling pathways able to sense it and activate an appropriate response. In between these, we identified Thioredoxin (TRX), a major antioxidant protein, and its endogenous inhibitor TXNIP. TXNIP bonds TRX by means of a disulfide bridge that saturates its active site. Such an interaction is redox-dependent as ROS can dissociate it resulting in a Thiol-Disulfide Interchange Reaction. Following a growing interest in finding subcellular targets and mechanisms linked to a possible cytoprotective effect of electromagnetic (EM) fields, we studied the influence of electric field over this system through a hybrid QM/MM approach. Results show a strong catalytic effect of the static electric field over the TRX-TXNIP complex dissociation reaction and a consistent products’ stabilization. A preliminary study on nanopulses also shows the effect to be significant in the transient period, making time a relevant variable only if the field amplitude is increased. These results are promising for a further characterization of this interaction mechanism, which could be the way (or one of many) in which EM fields might directly influence intracellular signaling pathways.