The aglycon, or so-called 'warhead' portion, of several potent 10-membered ring enediyne antitumor antibiotics contain dienonecarbamate and enediyne chromophores in an unusual bicyclic ring structure in which these two subunits are essentially orthogonal to each other. The circular dichroism (CD) spectra of the calicheamicin, esperamicin, and shisijimicin A families, all of which contain this bicyclic ring system, exhibit a characteristic negative exciton coupled CD at about 310 and 270 nm. This signature CD feature suggested the absolute stereochemical relationship between these chromophores as originally assigned and which was later confirmed by stereospecific total synthesis. Because of the unique nature of this chromophoric interaction and the importance of using this CD spectral feature in the assignment of the absolute stereochemistry of other related enediynes, we report here simulations of the CD spectra of the calicheamicin aglycon A, and of two other truncated models, B and C, by using density functional theory (DFT) and the DeVoe coupled oscillator approach. The DFT calculations provide a strong theoretical basis that the planar enediyne chromophore alone gives a negligible CD contribution, while that coming from the twisted dienonecarbamate is much more substantial. However, the shape and the largest part of the intensity of experimental CD spectrum can only be reproduced when the two unsaturated moieties are simultaneously present. Thus, the exciton coupling between the two chromophores provides the most important contribution to the experimental CD spectrum of calicheamicin. This conclusion is in full agreement with the results from the DeVoe calculation.