Thumbnail image of graphical abstract

Deoxythymidine, a deoxyribonucleoside, is presented separated into the high and low layers used by the ONIOM-ccCA methodology. The chemically relevant O4 position is highlighted, along with the adjacent atoms to be included in the high layer calculation. As presented by Amanda G. Riojas, Joshua R. John, T. Gavin Williams, and Angela K. Wilson on page 2590, by determining the proton affinities of deoxyribonucleosides and the location of preferred protonation sites, insight into the protonation of DNA may be attained, leading to a better understanding of a mechanism of DNA breakage that can result in carcinogenic or mutagenic effects.