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

[Image: see text] 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.