γ-环糊精和波尼松龙的相互作用分子动力学模拟和自由能计算

Molecular Dynamics Simulation and Free Energy Calculation on Interaction of γ-Cyclodextrin and Prednisolone

运用分子动力学(Molecular dynamics,MD)和MM-PBSA(molecular mechanics/Poisson Boltzmann surface area)相结合的方法预测了γ-环糊精(γ-cyclodextrin,γ-CD)和波尼松龙的包结模式.在MD模拟过程中,波尼松龙分别采用A环和D环两种取向从γ-CD大口端进入其空腔.在MD轨迹采样基础上,采用高效MM-PBSA方法计算了两种取向的包结自由能.结果表明,计算包结自由能值和实验包结自由能值非常吻合.进一步分析各个能量项,发现范德华相互作用能为包结的主要驱动力.通过比较两种取向的包结自由能大小,预测D环取向为优势包结模式.

The possible binding mode between γ-cyclodextrin（T-CD） and prednisolone was predicted by using molecular dynamics（MD） and MM-PBSA（ molecular mechanics/Poisson Boltzmann surface area） method. Prednisolone penetrated the cavity of γ-CD from the large rim by both A-ring orientation and D-ring orientation in the process of MD simulation. Based on the trajectories from MD simulations, the binding free energies of two orientations were calculated by using MM-PBSA technique. The results show that the calculated bind free energy is in well agreement with the experimental value. Through further analyzing each energy item, it is found that Van der Waals＇ interaction energy is the main driving force for the complexation. By comparing the bind free energies of two orientations, it was predicted that D-ring orientation is the preferential binding mode.