不同模拟方法研究β-环糊精识别对映体分子  

Study on chiral discrimination by β-cyclodextrin using different docking simulations

作　　者：刘铁兵[1] 张志强[2] 潘和蹇[2] 方慧生[3] 何华[2,4] 

机构地区：[1]浙江科技学院中德农产品加工工业研究院,浙江杭州310023 [2]中国药科大学分析化学教研室,江苏南京210009 [3]中国药科大学生生物信息学教研室,江苏南京210009 [4]药物质量与安全预警教育部重点实验室,江苏南京210009

出　　处：《计算机与应用化学》2011年第4期390-394,共5页Computers and Applied Chemistry

摘　　要：手性对映体分子的物理化学性质基本相同,其旋光性差异直接影响生物体内生理和药理的活性。本文以Builder和Discover-3模块为基础,在InsightII平台上模建并优化,采用Dock刚性、柔性对接及GOLD柔性对接的方法,模拟了β-环糊精识别手性对映体的能力。通过利用DMS程序计算环糊精分子溶剂的可接触表面,用SPHGEN程序计算,产生球集,形成环糊精分子活性位点的负像;在环糊精分子上打格点,计算格点能;采用格点的打分函数打分,分子对接,保存分数最高的对接结果等步骤;表明手性识别的预测率从高到低依次是GOLD对接,Dock柔性对接,Dock刚性生对接。由于刚性对接过程对映体分子保持刚性,导致手性识别效果最差,故分子柔性的作用不可忽视;GOLD对接在模拟环糊精对对映体手性识别方面要优于Dock对接模拟。因此,用GOLD对接建立了β-环糊精对对映体的手性识别模型,结合能越大,相互作用越强,形成的包合物越稳定。分析模型的结合能组分,以分子识别过程中的氢键作用为模型,则其手性识别预测结果正确率为45.5%;如以分子间氢键作用和范德华作用为预测模型,则其预测正确率为81.8%。表明手性识别的驱动力不仅有氢键的作用,也存在范德华力的作用。The chiral enantiomers molecular properties on chemical and physical is basically the same.Its optical rotation difference directly affects creature activity of physiological and pharmacological.Based on the Builder and Discover-3 modules,built and optimized on InsightⅡplatform mold, adopting intermolecular ligation methods of the Dock rigidity and flexibility and GOLD flexibility,this paper simulates theβ-cyclodextrins recognition chiral enantiomers ability.Calculating cyclodextrins molecular solvent contact surface by the use of DMS procedures,and calculating with SPHGEN procedures produce ball set,forming cyclodextrins molecular active site of negative image.Region points are marked in cyclodextrins molecules,and computed and scored by scoring function.From the steps of intermoleculars bind,and saving results of the highest numerical value, the results are obtained that the prediction recognition rate of chiral enantiomers molecule from high to low in turn is GOLD,Dock flexibility,and Dock rigid respectively.Since rigid docking process enantiomers molecules keep rigidness,resulting in chiral poor recognition effect,the role of molecular flexiblity should not be ignored.The GOLD docking in simulation of cyclodextrins enantiomers chiral recognition is superior to the Dock docking.Therefore with the GOLD docking the chiral recognition model to establishβ-cyclodextrins,the greater enantiomers binding-energy,the stronger interaction,and the more stable the formed closure content.Analysing model of binding-energy components,and molecular recognition process of the hydrogen bonding interaction as model,the chiral recognition accuracy of prediction is 45.5%.With the hydrogen bonding interaction between the molecules and van der Waals role for forecasting model,chiral recognition accuracy is 81.8%.The results show that the driving force of chiral recognition include not only hydrogen bond energy,but also Van der Waals energy.

关 键 词：GOLD DOCK Β-环糊精 手性识别 模拟 

分 类 号：R917[医药卫生—药物分析学] O641.3[医药卫生—药学]