中文摘要：

使用分子动力学模拟结合自由能计算的方法在原子水平上研究了谷胱甘肽与α-,β-和γ-环糊精的包结模式,计算了谷胱甘肽与3种环糊精之间6种可能包结过程的自由能变化.结果表明,谷胱甘肽的谷氨酸残基从α-环糊精大口端进入空腔最终形成的包结复合物最稳定;在该复合物中,谷氨酸残基的亚甲基链部分被完全包结在疏水空腔中,其氨基与羧基位于与α-环糊精的小口端,并与环糊精的伯羟基形成了氢键,同时半胱氨酸中的巯基位于环糊精的大口端,得到了有效的保护.因此,疏水相互作用和氢键相互作用构成了包结的主要驱动力.β-环糊精的优势包结模式与α-环糊精类似,但形成复合物的稳定性次之,而γ-环糊精由于空腔较大,优势的包结模式是谷氨酸残基从γ-环糊精小口端进入空腔,但所形成的复合物结构的稳定性最弱.

英文摘要：

By using molecular dynamics simulations combined with free energy calculations,the inclusion modes of α-,β-,and γ-cyclodextrins（ CDs） with glutathione（ GSH） in an aqueous environment were investigated at the atomic level. The free-energy changes for the six possible inclusion processes of the three types of CDs with GSH were calculated. The results show that the inclusion complex formed by GSH and α-CD with the orientation that the glutamic acid（ Glu） residue entering from the secondary rim of the CD is the most energetically favored,wherein the methylene chain of the Glu is completely buried in the cavity of α-CD,and three hydrogen bonds are formed between α-CD and GSH. It is worth noting that in this most stable complex structure,the sulfhydryl group of GSH is included at the secondary rim,thereby being protected by α-CD.Moreover,hydrophobic and hydrogen-bonding interactions constitute the main driving force responsible for the formation of the host-guest complex. The favorable inclusion mode of GSH with β-CD is similar to that with α-CD,but the corresponding complex of the former is less stable than that of the latter. On the contrary,forγ-CD,the favorable orientation is that the Glu residue enters the cavity from the primary side of the CD. From the free-energy calculations reported herein,the relative binding affinity with GSH follows the ranking orderα-CD〉β-CD〉γ-CD.