The possible binding modes between β-cyclodextrin (β-CD) and steroids were predicted by using molecular dynamics (MD) and MM-PBSA (molecular mechanics/Poisson Boltzmann surface area) methods. The guest molecules with two types of binding modes both form stable complexes with β-CD by heavy atom root mean square deviation (RMSD) analysis. Based on the trajectories from MD simulations, the binding free energies for the two types of binding modes were calculated by using the MM-PBSA method. The computed results show that the main impetus for complexes lies in the van der Waals’ interaction between β-CD and three steroids, but the solvation energy and the entropy change produce adverse effect on the complexes. Through further analyzing the averaged conformations and binding free energies of the β-CD and three steroids, it was found that D-up orientation was the preferential binding mode for prednisolone, whereas A-up orientation was the preferential binding mode for ethinyloestradiol and estriol. By comparing the theoretical binding free energies of β-CD with the three steroids, it was obtained that the stability of the inclusion complexes is ethinyloestradiol＞estriol＞prednisolone, which is in good agreement with the experimental result.

Key words: MM-PBSA, molecular dynamics, β-cyclodextrin, steroid