Over the years, various approaches have been developed to calculate CD spectra for DNA, ranging from empirical methods to advanced quantum mechanical calculations. In 2015, Monari et al. proposed a multiscale approach to calculate the CD spectra of B-DNA. Their method combined quantum mechanical calculations of individual nucleobases on snapshots selected from molecular dynamics simulations. Excited states of individual base pairs were obtained using time-dependent DFT in a QM/MM setting and used to build a Frenkel exciton model. This approach allowed them to account for the effects of structural fluctuations on the exciton coupling between DNA bases and provided a more accurate representation of the coupling compared to the dipole approximation. This approach was then successfully used to investigate the CD spectra of DNA G-quadruplexes. The authors demonstrated that their method accurately reproduces experimental CD spectra for various G-quadruplex topologies, highlighting the significant influence of G-tetrad stacking interactions on spectral features. The approach successfully distinguishes between parallel and antiparallel G-quadruplex arrangements while claiming that loop nucleotides have minimal impact on the overall spectra. Aside from the excitonic model, several approaches have been used to compute CD spectra of DNA by finding the smallest minimal model to reproduce experimental methods. We have for instance shown that a dimer of base-pair representative of a double strand of 20 base pairs can be used to reproduce accurately the experimental spectra. We then successfully applied this approach to reproduce the decrease in intensity observed in nucleosomal DNA upon wrapping around the nucleosome. The choice of this small model was obviously guided by the limitation in system size that could be treated with the software available at that time. Given the general performance of VeloxChem on modern hardware and the GPU implementation presented here, we make an attempt to push the boundaries of DNA modeling and revisit the case of the G-quadruplex.