Denaturation of dsDNA Induced by Specific Major Groove Binding of Cadmium Ion to Thymine

The toxicity of cadmium causes varying degrees of risk to organisms. The underlying mechanism has been conventionally attributed to Cd 2+ -ion-induced oxidative stress. Here, we propose that the Cd 2+ ion directly and stably binds with the thymine specifically in the major groove and causes denaturation of dsDNA. Using molecular dynamics simulations, it was found that the Cd 2+ ion preferred to bind to the thymine exposed in the major groove. This then destroyed the hydrogen bonds between adenine and thymine, resulting in a mismatched structure of dsDNA. Our findings are expected to promote the understanding of cadmium-induced direct destruction of genomic stability and may also be helpful for the facilitation of the experimental detection of the binding sites.