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

A molecular docking method that predicts the lowest energy geometries of in clusion complexes between host and guests was developed and tested, in comb ination with a new simple empirical function that estimates the free energy of binding. The total interaction energies of the host-guest inclusion com plexes were optimized using a genetic algorithm (GA). The docking method wa s applied to 43 complexes of cl-cyclodextrin (alpha -CD) and mono- or 1,4-d isubstituted benzenes with known binding constants. The new simple empirica l free energy function was calibrated by the 43 docked complex structures a nd gave a good relationship between the predicted binding constants and the observed values. (C) 2001 Elsevier Science B.V. All rights reserved.