The human adenoviral (Ad) life cycle is divided into early and late phases.In the early phase, the virus optimizes the host environment for its replication. Once the virus starts replicating its genome, the life cycle enters the late phase. Many viral proteins, including capsid proteins, are encoded in the viral late gene region and expressed during the late phase. At the end of the late phase, the viral genomes are encapsidated to form the infectious viral particles. This encapsidation process is a critical step which requires threshold levels of progeny viral genomes and capsid proteins. To optimize assembly of viral particles, the viral late gene transcription and genome encapsidation processes must proceed as ordered events, i.e. they must be precisely regulated. In this scenario, the activation of the encapsidation pathway behaves like a classic genetic switch. Previous studies have shown that two viral proteins, IVa2 and L4-22K, recognize a specific DNA binding site within both the promoter region of viral late genes and the packaging sequence (PS) DNA which are required for encapsidation. However, the DNA architecture is different in these two regions. Multiple copies of this specific binding site have been identified in the PS DNA while only a single copy has been identified in the late gene promoter. We hypothesize the interaction of IVa2, L4-22K, and these specific DNA binding sites regulates the viral decision to initiate encapsidation. To develop a predictive model to describe this process, we have initiated a physical-chemical study of the assembly of the IVa2 and L4-22K proteins on these specific DNA sequences.