Molecular interactions of α-cyclodextrin inclusion complexes using a genetic algorithm

Abstract Molecular interactions of inclusion complexes of mono- or 1,4-disubstituted benzenes and α-cyclodextrin have been studied in this paper. Two types of energy terms were considered in the total interaction energies, non-bonded term and desolvation term, and minimized by a genetic algorithm (GA). Using the consistent force field (CFF91), the non-bonded energies between all pairs of atoms in different molecules were determined by a Coulomb potential term for electrostatic interactions and a Lennard-Jones potential for van der Waals interactions. The desolvation energy term was modeled by a simple constant term corresponding to a penalty when polar atoms are placed in the hydrophobic cavity. The total interaction energies for 15 inclusion complexes with experimental association constants (ln  K ) were optimized by the GA method. Linear regression analysis of the observed association constants against the total energies was performed. It was found that the interaction energies of these complexes obtained by the simple interaction energy model could be correlated with their experimental association constants, and also the desolvation term should be included.