【作者】 张静；

【导师】 许佩军；

【作者基本信息】 辽宁师范大学 ， 粒子物理与原子核物理， 2011， 硕士

【摘要】 对蛋白质折叠的研究是生命科学的前沿课题,近些年来利用计算机模拟蛋白质折叠已经成为一种重要的研究手段.但是许多人们感兴趣的生物现象都发生在毫秒甚至更长的时间内,而对于较大的生物体系的全原子模拟其模拟时间很难达到.为了克服这个缺陷,同时又要保证计算精度,我们针对不同的蛋白质分子结构建立了合适的刚体动力学模型,然后利用TINKER软件包模拟蛋白质的折叠过程.本文的主要内容包括:(1)对丙氨酸饱和多肽链的折叠进行分子动力学模拟,根据丙氨酸饱和多肽链的分子结构划分了两种刚体结构,基于刚体动力学模型对17个丙氨酸饱和多肽链的折叠做分子动力学模拟,并选择在五种不同的力场(AMBER99、CHARMM27、OPLSAA、AMBER99SB和AMOEBAPRO)下分别进行.然后改变丙氨酸饱和多肽链中丙氨酸残基的数目,选择9个和13个丙氨酸饱和多肽链基于刚体动力学模型进行同等条件下的分子动力学模拟.需要注意的是这里所有刚体动力学的模拟结果都要与全原子模拟结果做对比,基于不同刚体结构的动力学模拟结果也要进行相应的对比.研究表明刚体动力学模型对丙氨酸饱和多肽链折叠的模拟不仅与刚体结构划分、力场的选择有关,还与残基数目的多少有关.(2)为了进一步拓展刚体动力学模型,本文又对2I9M饱和多肽链的折叠进行了分子动力学模拟,根据2I9M饱和多肽链的分子结构划分了两种刚体结构,并在四种不同的力场(AMBER99、CHARMM27、OPLSAA、AMBER99SB)下分别进行刚体动力学模拟α螺旋结构,并将刚体动力学模拟的结果与全原子模拟的结果进行了对比.研究结果表明,基于刚体动力学模型对2I9M饱和多肽链折叠的模拟中没有得到α螺旋结构,对其折叠模拟的研究还需要进一步的探索.更多还原

【Abstract】 The research of protein folding is a new frontier in life science. In recent years , protein folding simulation with computers has become an important research mean. But many phen omena of interest in biological occur in milliseconds or even more long time. For a larger biol ogical system, it is hard to reach all-atom molecule simulation time. In order to overcome the defects and assure the calculation precision at the same time, we according to different protein molecule structure to establish appropriate rigidbody dynamics models, using the TINKER process packages to simulate protein folding. The main content of this article include :(1)We make molecular dynamics simulation about saturated polyalanine folding. According to molecular structure, saturated polyalanine can be substructured into two different rigidbody dynamics models. We make molecular simulations aboutα-helix of seventeen saturated polyalanine based on the rigidbody dynamical models in five different force fields (AMBER99, CHARMM27, OPLSAA, AMBER99SB and AMOEBAPRO), respectively. Change the number of residues for saturated polyalanine, then we make molecular simulations aboutα-helix of nine and thirteen saturated polyalanine based on the rigidbody dynamical models in the same condition. We compare the results with those of the all-atom simulations, and the results of simulations among rigidbody models. All results show that, within the framework of rigidbody dynamical model, theα-helix not only depends on the definition of rigidbody and the force fields , but on the the number of residues for saturated polyalanine.(2)In order to further expand the rigidbody dynamics model, we make molecular dynamics simulation about saturated 2I9M polypeptide chain folding. According to molecular structure, saturated 2I9M polypeptide chain can be substructured into two different rigidbody models. Within four different force fields (AMBER99, CHARMM27, OPLSAA and AMBER99SB), we make molecular simulations aboutα-helix of saturated polyalanine based on the rigidbody dynamical models. We compare the results with those of the all-atom simulations. All results show that, within the framework of rigidbody dynamical models, saturated 2I9M polypeptide chain don’t formα-helix, the research of simulation still needs further exploration.更多还原