The homodimeric catabolite activator protein (CAP) is a bacterial DNA binding transcription regulator whose activity is controlled by the binding of the intracellular mediator cyclic adenosine monophosphate (cAMP). Each CAP subunit consists of a cyclic nucleotide and a DNA binding domain. Here, we investigate the structural features of the ligand-bound CAP in aqueous solution by molecular dynamics simulations based on the available X-ray structures (Passner et al. J. Mol. Biol. 2001, 304, 847-859 and Chen et al. J. Mol. Biol. 2001, 314, 63-74). Our calculations suggest that the homodimer in solution assumes a symmetric arrangement in which both DNA binding domains are separated from the respective cyclic nucleotide binding domains by a cleft. This contrasts with the X-ray structure, which exhibits instead an asymmetric conformation. On the basis of electrostatics calculations, we propose that the symmetric structure in solution may be an important feature for DNA molecular recognition.