DNA构象在盐溶液中的动力学模拟转变研究
发布时间：2018-07-20 16:40
【摘要】：由脱氧核糖核酸聚合形成的高分子脱氧核糖核酸链,被称为DNA。DNA作为生命体中的重要部分,其在生命活动中扮演着至关重要的作用,是动植物细胞内携带遗传信息的关键物质。DNA作为遗传信息的记录者,以及生命体功能的指导者,其在细胞内的结构是动态可变的。众多研究表明DNA的构象变化范围极广,小到在当前构象下的微扰动,大到DNA的解旋等。DNA有着许多构象,其构象的稳定性不仅取决于包含了DNA序列和剪辑的化学修饰的化学成分作用,同时还受到溶液条件的影响。由于在DNA的复制、转录、翻译过程中通常会有规则性的构象变化发生,研究者认为DNA是通过构型的变化发挥其生理功能。此外,DNA本身在物理学上视为一种通用的分子设计纳米尺度结构,由于通过其适当的序列排列可以使DNA列折叠成定义明确的二级结构,DNA被认为有望发展为纳米仪器的移动部件,如纳米钳子。并可以通过DNA不同的构象之间的转换来驱动基于DNA的可控分子机械。因此人们对DNA的构象转变研究投予了更多的关注。DNA的B构象是DNA在生理条件下的热力学最稳态,然而DNA的双螺旋结构也赋予了其足够的结构灵活性。而结构较为紧凑的A构象被认为不仅在基因的表达中起着重要作用,同时也在某些蛋白质-DNA复合物中作为识别基序,DNA的A/B构象相互转变过程被认为是蛋白-DNA复合识别的模式之一,同时也被认为是推动DNA进行自组装,以及通过病毒蛋白壳体的主要推动力之一。正因如此,在诸多DNA的构象研究中,关于A-B构象变化的研究是极为广泛的。现有的研究表明,溶液中的碱金属平衡离子会对DNA的A→B构象转变过程起到一个阻碍的作用。且在实验中发现了A-DNA构象可稳定存在于高浓度NaCl水溶液中。因此我们猜想可通过模拟得到高浓度盐溶液中初始A-DNA构型随时间保持构型稳定的结果。本文基于分子动力学原理,选用GROMACS5.1.4软件包,对标准构型的A-DNA和B-DNA在高浓度盐溶液中的构象变化进行模拟分析。进行了以下研究:1、对当今各种分子动力学模拟力场进行比较,得出了Charmm36力场最为适用于这一体系。2、对Na、K、Rb等碱金属离子进行了模拟比较,发现在阻碍构象变化能力上KRbNa。3、对大于1M的不同浓度离子体系进行模拟,发现在3M浓度区间时有较稳定的类A构象的存在。而在较低盐浓度溶液体系中,初始B构象保持较稳定状态,而A构象向B构象转变,与实验数据相吻合。对构象进行分析发现Na+离子在DNA大沟的聚集可能是阻止构象转变的重要原因。这一研究丰富了人们对于DNA分子在盐溶液下的构象转变的分子动力学模拟认识。然而需要注意当前分子动力学模拟的力场参数还尚未完善,表现在多种力场下的模拟最终构象均非A构象,部分DNA分子在模拟过程中出现碱基对分离等方面。
[Abstract]:The high molecular deoxyribonucleic acid chain formed by deoxyribonucleic acid polymerization is called DNA.DNA as an important part of life and plays a vital role in life activities. DNA is the key material carrying genetic information in plant and animal cells. As the recorder of genetic information and the guide of biological function, the structure of DNA in cells is dynamic and variable. Numerous studies have shown that DNA has a wide range of conformational variations, ranging from microperturbations in the current conformation to the unwinding of DNA. DNA has many conformations. The stability of the conformation depends not only on the chemical composition of the modified DNA sequences and clips, but also on the solution conditions. Because there are regular conformation changes in the process of DNA replication, transcription and translation, researchers believe that DNA exerts its physiological function through structural changes. In addition, DNA itself is seen in physics as a generic molecular design nanoscale structure, and since DNA columns can be folded into well-defined secondary structures through its proper sequence alignment, DNA is expected to develop into a moving component of nanometers. Such as nano-pliers. DNA based controllable molecular machinery can be driven by the conversion of different conformation of DNA. Therefore, more attention has been paid to the conformational transformation of DNA. The B conformation of DNA is the most stable thermodynamics of DNA under physiological conditions. However, the double helix structure of DNA also gives it sufficient structural flexibility. The compact A conformation is thought to play an important role not only in gene expression, but also in gene expression. At the same time, in some protein-DNA complexes, the process of A- / B conformational transformation for recognizing motif DNA is considered to be one of the patterns of protein-DNA complex recognition, and it is also considered to promote DNA self-assembly. And one of the main driving forces through viral protein shells. For this reason, the study of A-B conformation change is very extensive in many conformation studies of DNA. It has been shown that the equilibrium ions of alkali metals in solution may hinder the conformational transition of DNA. It was found that A-DNA conformation was stable in high concentration NaCl aqueous solution. Therefore, we suppose that the initial A-DNA configuration in the solution of high concentration salt can be obtained by simulation, and the initial A-DNA configuration remains stable with time. Based on the principle of molecular dynamics, the conformation changes of A-DNA and B-DNA of standard configuration in high concentration salt solution were simulated and analyzed by using GROMACS5.1.4 software package. The following studies have been carried out: 1. By comparing the force fields of various molecular dynamics simulations, the Charmm36 force field is found to be the most suitable for this system, and the alkali metal ions, such as Najikanrb, are simulated and compared. It is found that KRbNa.3simulates ion systems with different concentrations more than 1m in the ability to hinder conformation change. It is found that there is a stable A-like conformation in the concentration range of 3M. In the solution with lower salt concentration, the initial B conformation remained stable, while the A conformation changed to the B conformation, which was consistent with the experimental data. The conformation analysis shows that the aggregation of Na ions in the DNA furrow may be an important reason to prevent the conformation transition. This study enriches the molecular dynamics simulation of the conformation transition of DNA molecules in salt solution. However, it is necessary to note that the force field parameters of molecular dynamics simulation are not perfect at present. The final conformation of simulation under various force fields is not A-conformation, and some DNA molecules appear base pair separation in the simulation process.
【学位授予单位】：山西师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O629.74
本文编号：2134126
[Abstract]:The high molecular deoxyribonucleic acid chain formed by deoxyribonucleic acid polymerization is called DNA.DNA as an important part of life and plays a vital role in life activities. DNA is the key material carrying genetic information in plant and animal cells. As the recorder of genetic information and the guide of biological function, the structure of DNA in cells is dynamic and variable. Numerous studies have shown that DNA has a wide range of conformational variations, ranging from microperturbations in the current conformation to the unwinding of DNA. DNA has many conformations. The stability of the conformation depends not only on the chemical composition of the modified DNA sequences and clips, but also on the solution conditions. Because there are regular conformation changes in the process of DNA replication, transcription and translation, researchers believe that DNA exerts its physiological function through structural changes. In addition, DNA itself is seen in physics as a generic molecular design nanoscale structure, and since DNA columns can be folded into well-defined secondary structures through its proper sequence alignment, DNA is expected to develop into a moving component of nanometers. Such as nano-pliers. DNA based controllable molecular machinery can be driven by the conversion of different conformation of DNA. Therefore, more attention has been paid to the conformational transformation of DNA. The B conformation of DNA is the most stable thermodynamics of DNA under physiological conditions. However, the double helix structure of DNA also gives it sufficient structural flexibility. The compact A conformation is thought to play an important role not only in gene expression, but also in gene expression. At the same time, in some protein-DNA complexes, the process of A- / B conformational transformation for recognizing motif DNA is considered to be one of the patterns of protein-DNA complex recognition, and it is also considered to promote DNA self-assembly. And one of the main driving forces through viral protein shells. For this reason, the study of A-B conformation change is very extensive in many conformation studies of DNA. It has been shown that the equilibrium ions of alkali metals in solution may hinder the conformational transition of DNA. It was found that A-DNA conformation was stable in high concentration NaCl aqueous solution. Therefore, we suppose that the initial A-DNA configuration in the solution of high concentration salt can be obtained by simulation, and the initial A-DNA configuration remains stable with time. Based on the principle of molecular dynamics, the conformation changes of A-DNA and B-DNA of standard configuration in high concentration salt solution were simulated and analyzed by using GROMACS5.1.4 software package. The following studies have been carried out: 1. By comparing the force fields of various molecular dynamics simulations, the Charmm36 force field is found to be the most suitable for this system, and the alkali metal ions, such as Najikanrb, are simulated and compared. It is found that KRbNa.3simulates ion systems with different concentrations more than 1m in the ability to hinder conformation change. It is found that there is a stable A-like conformation in the concentration range of 3M. In the solution with lower salt concentration, the initial B conformation remained stable, while the A conformation changed to the B conformation, which was consistent with the experimental data. The conformation analysis shows that the aggregation of Na ions in the DNA furrow may be an important reason to prevent the conformation transition. This study enriches the molecular dynamics simulation of the conformation transition of DNA molecules in salt solution. However, it is necessary to note that the force field parameters of molecular dynamics simulation are not perfect at present. The final conformation of simulation under various force fields is not A-conformation, and some DNA molecules appear base pair separation in the simulation process.
【学位授予单位】：山西师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O629.74
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