Significance Circadian rhythms enable organisms to adapt to the 24-h day/night cycle. The importance of these rhythms is evident from their prevalence across the kingdoms of life and their dysregulation in many diseases. The core clock of the cyanobacterium Synechococcus elongatus serves as a paradigm for molecular studies of circadian rhythms because its oscillations can be reconstituted in vitro. There is evidence that the action of KaiC, the central component of the oscillator, depends critically on whether its active sites bind ADP or ATP, metabolites that function as the energy currency in cells. Here, we use molecular dynamics simulations to develop an atomic-resolution picture of ADP release and, in turn, hypotheses for the regulation of ADP/ATP exchange.