Interaction between a transmembrane pore protein a-hemolysin and a cyclic oligosaccharide beta-cyclodextrin results in a system that can be viewed from several different perspectives-as an ion channel modified by a noncovalent adapter, thus providing a pivotal building block for the novel single molecule sensor devices, as a model protein-carbohydrate complex, whose structural, dynamical and energetic properties can be helpful in understanding the mechanisms of protein-carbohydrate recognition in biological systems, and as an example of a self-assembling supramolecular system. The detailed understanding of mechanisms of intermolecular interactions in such complexes is, therefore, of wide interest. We have performed a set of molecular dynamics (MD) simulations (20 ns of total reported simulation time) of a beta-cyclodextrin (betaCD) molecule confined inside the lumen of the alpha-hemolysin channel (alphaHL). For comparison, the 8 ns dynamics of a free betaCD in bulk aqueous solution was also performed. A detailed analysis of the interaction energetics and conformational flexibility of betaCD inside the water-protein channel and in water is provided. The intra- and intermolecular hydrogen bonding in the complex and in aqueous solution is elucidated and implications of the confined environment on the dynamics of the cyclodextrin molecule are discussed. We have found that contributions to the binding energy due to the nonpolar solvation and the van der Waals interactions between alpha-hemolysin and beta-cyclodextrin are favorable for binding. The equilibrated configurations with betaCD residing in the vicinity of Met113 residue of alphaHL protein and with wider rim oriented toward the trans side of the membrane are the most favorable in terms of both interaction and binding energies. This result is in accord with the previous suggestion based on the indirect experimental observations. The formation of the complex is characterized by van der Waals contacts with Met113, Thr115, and Thr145 residues and electrostatic interactions with Glu111 and Lys147. The hydrogen-bonding pattern comprises a few direct bonds with Thr115, Thr145 and several water-mediated hydrogen bonds with Thr115, Thr117, Thr145, and Lys147. Mutation of these residues in addition to Met113, which has already been studied systematically, is expected to alter the binding affinity to betaCD. Conformational flexibility of the macroring of betaCD is considerably reduced in the confined environment of the channel. The conformational motion of side groups of alpha-hemolysin at the binding site is also affected by the presence of betaCD.