Molecular docking of α-cyclodextrin inclusion complexes by genetic algorithm and empirical binding free energy function

A molecular docking method that predicts the lowest energy geometries of inclusion complexes between host and guests was developed and tested, in combination with a new simple empirical function that estimates the free energy of binding. The total interaction energies of the host–guest inclusion complexes were optimized using a genetic algorithm (GA). The docking method was applied to 43 complexes of α-cyclodextrin (α-CD) and mono- or 1,4-disubstituted benzenes with known binding constants. The new simple empirical free energy function was calibrated by the 43 docked complex structures and gave a good relationship between the predicted binding constants and the observed values.