【作者】 赵宏璐；

【导师】 徐德昌；

【作者基本信息】 哈尔滨工业大学 ， 生物化工， 2008， 硕士

【摘要】 环二肽是环肽中氨基酸个数最少的一类化合物,具有明显的生理活性,在生物体的生命活动中扮演着极其重要的角色。环二肽稳定性的研究对药物合成以及生物活性机理的探究具有重要的指导意义。本文构建了含赖氨酸、精氨酸、组氨酸的环二肽及其相应直链肽的构型,对其进行量子化学计算,分析分子的稳定性。在此基础上,对这些环二肽与十二烷基磺酸钠(SDS)的相互作用进行理论化学研究。对含赖氨酸、精氨酸、组氨酸的环二肽进行几何全优化,初始构型中的船式六圆环转变为刚性平面环;以含lys二肽为例分析比较了含赖氨酸的环二肽和相应直链肽优化后的能量值。对不同氨基酸组成的含lys二肽,能量值的大小顺序都是环二肽>H型直链二肽>coated型直链二肽。lys-gln和lys-asn的二肽能量差明显小于大多数二肽,lys-glu和lys-asp的二肽能量差明显大于大多数二肽。coated型直链肽优化后,呈现出β片层结构。影响二肽能量的主要因素是侧链氨基酸上R基团的不同。本文对计算所得的二肽与DS-相互作用的的结合能进行分析比较。结果表明,含赖氨酸二肽中,lys-pro环二肽比相应直链二肽更容易与SDS结合。含精氨酸二肽中有7种二肽的相应环二肽比直链二肽更容易与SDS结合,含组氨酸二肽中有10种二肽的相应环二肽比直链二肽更容易与SDS结合。其余的二肽相反。从结合值的大小来看,这三类碱性氨基酸二肽与SDS作用结合的容易程度顺序为:组氨酸>赖氨酸>精氨酸。对与SDS作用后的直链二肽进行二级结构预测,根据构型中的二面角φ和ψ值作出拉氏构象图,根据图中散点位置归类,lys-glu、lys-his、arg-his、his-pro、his-trp组成的直链二肽没有显著的结构特征,其余的直链二肽均表现为β片层结构。更多还原

【Abstract】 Cyclic dispeptide only contains two amio acid, it is the smallest one in cyclic peptide family, with prominent physiological activity and play an important role in life movement. The research on the stability of dispeptide has directive significant in medicine synthesis and biological activity principium. This article established the configuration of cyclic dispeptides containing Lys, Arg, His and their corresponding straight dispeptides. which were calculated by using quantum chemical method, and analysised. Basis on this, we did research on the interaction between these dispeptides and Sodium dodecyl sulfate(SDS).In the total geometry optimization for the cyclic dispeptides containing Lys, Arg, His. The boat configuration hexahydric ring in the initial structure changed to flat ring. Take the dispeptides containing lys for example, energy of cyclic dispeptides and corresponding straight dispeptides were compared after optimization. For the dispeptides containing lys with different amino acid, the energy orders are the same: cyclic dispeptides>H form straight dispeptides>coated form straight dispeptides. The differ energy of lys-gln and lys-asn were lower than most of dispeptides, while differ energy of lys-glu and lys-asp were higher than most of dispeptides. The optimized coated form straight dispeptide showed theβsheet structure. The main influence element is the R residue of amino acid.The binding energies between dispeptides and DS- are also compared which were accurate computed. The results showed that cyclo(lys-pro) was easer to bind to SDS than H form(lys-pro). Their were seven cyclo dispeptides containing Arg easer to bind to SDS than corresponding straight dispeptides, while the number is 10 for dispeptides containing His.The easy degree of the interaction between these three kinds of alkaline amino acid and SDS is: his>lys>arg.We predicted the secondary structure of straight diapeptides which were interacted with DS- and drew the Ramachandran plot due to the dihedral angelφandψ. In the plot we found that there are no special structure type for lys-glu, lys-his, arg-his ,his-pro, his-trp, other dispeptides were showedβsheet structure.更多还原