Application of Multiple Topology λ-Dynamics to a Host−Guest System: β-Cyclodextrin with Substituted Benzenes

The λ-dynamics approach to free energy simulations has been applied the host−guest system of β-cyclodextrin interacting with a series of monosubstituted benzenes. Each ligand was explicitly represented, and restraining potentials [Banba, S.; Brooks, C. L., III, J. Chem. Phys. 2000, 113, 3423] were used to restrain the unselected ligands in nearly binding conformations. Using biasing potentials to enhance convergence, excellent correlation between the free energies derived from λ-dynamics and free energy perturbation results is obtained. Effects of the strength of the restraining potentials and bias potentials on the sampling of the conformational space have been examined. Ligands with smaller substituents explored alternate binding orientations in the presence of weak and moderate restraining potentials.