Modelling of molecular interactions and inclusion phenomena in substitutedbeta-cyclodextrin: From simple probes to proteins

The ability of beta-cyclodextrin (PCD) to form stable complexes with alpha- interferon was investigated. By using simple molecular mechanics approach i nteraction energy profiles of simple probes passing the center of PCD ring cavity along the main molecular symmetry axis were evaluated first. A compu tational study of host-guest inclusion complexes between PCD and L-alpha-am inoacids and some selected pentapeptides was also carried out and aimed at understanding the nature of the driving forces and mechanism, leading to th eir formation. Relative complexation energies for the complexes and the sol vation Gibbs free energies for single L-alpha-aminoacids were calculated. B oth the aminoacid residue inside the PCD cavity and neighbouring residues w ere found to contribute to the stabilization of beta CD complexes with the side-chain of aminoacids present on the surface of alpha-interferon. The mo st appropriate number of host PCD molecules for the encapsulation in the fi rst shell of one alpha-interferon molecule resulted to be 25.