2种方法对不同pH下猪胰岛素结构的分子动力学模拟  

Conformation analysis of porcine insulin by using two methods of molecular dynamics simulation at various pH values

作　　者：马宁[1] 余劲聪[1] 方柏山[1,2] 

机构地区：[1]福建省高校工业生物技术重点实验室(华侨大学),福建厦门361021 [2]厦门大学生物化工学院化学工程与生物工程系,福建厦门361005

出　　处：《计算机与应用化学》2011年第9期1107-1111,共5页Computers and Applied Chemistry

基　　金：国家自然科学基金资助项目(21076172)

摘　　要：为了研究猪胰岛素单体在不同pH下的动态变化,本文从已有的NMR实验数据出发,通过2种不同的方法对胰岛素单体进行了MD模拟,方法1在已知不同pH下晶体结构及氨基酸侧链质子化状态时进行模拟,方法2为从特定晶体结构出发,通过设定部分氨基酸侧链的质子化状态来模拟不同pH下蛋白的结构变化。方法2在某些文章中已被使用,但是没有人探索过该方法是否具有普适性。本文的研究表明,方法2可以比较好地模拟不同pH下蛋白的结构变化,该方法可能具有普适性。针对胰岛素B链C末端的PheB24和PheB25的结构变化,PheB25的侧链在pH为6左右时会移动到胰岛素表面,同时PheB24处的β折叠会转变为无规卷曲,这一结果表明该处的β折叠可能并不是胰岛素单体聚合为二聚体的必要条件。In order to study structure flexibility of porcine insulin monomer under different pH, two methods are tested in this paper, the first method is to carry out MD simulation based on structures acquired under specified pH with determined ionization states of side chains, the second method is to set the ionization states of side chains to simulate insulin under different pH. The second method has been applied in some paper but none has tested whether this method has universality or not. In this paper, satisfying results in simulating insulin under different pH are obtained by the second method, and thus the universality of this method is conformed, at least to some extent. The results show that the side chain of PheB25 move to the surface of insulin at approximately pH 6.0, meanwhile J3-sheet at PheB24 turns to coil, and this indicates that 13-sheet may be not essential in the process of aggregation of monomer into dimer.

关 键 词：猪胰岛素 二级结构 活性中心:分子动力学模拟 NAMD 

分 类 号：TQ015.9[化学工程] TP391.9[自动化与计算机技术—计算机应用技术]