DNA構(gòu)象在鹽溶液中的動力學(xué)模擬轉(zhuǎn)變研究
發(fā)布時間：2018-07-20 16:40
【摘要】：由脫氧核糖核酸聚合形成的高分子脫氧核糖核酸鏈,被稱為DNA。DNA作為生命體中的重要部分,其在生命活動中扮演著至關(guān)重要的作用,是動植物細胞內(nèi)攜帶遺傳信息的關(guān)鍵物質(zhì)。DNA作為遺傳信息的記錄者,以及生命體功能的指導(dǎo)者,其在細胞內(nèi)的結(jié)構(gòu)是動態(tài)可變的。眾多研究表明DNA的構(gòu)象變化范圍極廣,小到在當前構(gòu)象下的微擾動,大到DNA的解旋等。DNA有著許多構(gòu)象,其構(gòu)象的穩(wěn)定性不僅取決于包含了DNA序列和剪輯的化學(xué)修飾的化學(xué)成分作用,同時還受到溶液條件的影響。由于在DNA的復(fù)制、轉(zhuǎn)錄、翻譯過程中通常會有規(guī)則性的構(gòu)象變化發(fā)生,研究者認為DNA是通過構(gòu)型的變化發(fā)揮其生理功能。此外,DNA本身在物理學(xué)上視為一種通用的分子設(shè)計納米尺度結(jié)構(gòu),由于通過其適當?shù)男蛄信帕锌梢允笵NA列折疊成定義明確的二級結(jié)構(gòu),DNA被認為有望發(fā)展為納米儀器的移動部件,如納米鉗子。并可以通過DNA不同的構(gòu)象之間的轉(zhuǎn)換來驅(qū)動基于DNA的可控分子機械。因此人們對DNA的構(gòu)象轉(zhuǎn)變研究投予了更多的關(guān)注。DNA的B構(gòu)象是DNA在生理條件下的熱力學(xué)最穩(wěn)態(tài),然而DNA的雙螺旋結(jié)構(gòu)也賦予了其足夠的結(jié)構(gòu)靈活性。而結(jié)構(gòu)較為緊湊的A構(gòu)象被認為不僅在基因的表達中起著重要作用,同時也在某些蛋白質(zhì)-DNA復(fù)合物中作為識別基序,DNA的A/B構(gòu)象相互轉(zhuǎn)變過程被認為是蛋白-DNA復(fù)合識別的模式之一,同時也被認為是推動DNA進行自組裝,以及通過病毒蛋白殼體的主要推動力之一。正因如此,在諸多DNA的構(gòu)象研究中,關(guān)于A-B構(gòu)象變化的研究是極為廣泛的�，F(xiàn)有的研究表明,溶液中的堿金屬平衡離子會對DNA的A→B構(gòu)象轉(zhuǎn)變過程起到一個阻礙的作用。且在實驗中發(fā)現(xiàn)了A-DNA構(gòu)象可穩(wěn)定存在于高濃度NaCl水溶液中。因此我們猜想可通過模擬得到高濃度鹽溶液中初始A-DNA構(gòu)型隨時間保持構(gòu)型穩(wěn)定的結(jié)果。本文基于分子動力學(xué)原理,選用GROMACS5.1.4軟件包,對標準構(gòu)型的A-DNA和B-DNA在高濃度鹽溶液中的構(gòu)象變化進行模擬分析。進行了以下研究:1、對當今各種分子動力學(xué)模擬力場進行比較,得出了Charmm36力場最為適用于這一體系。2、對Na、K、Rb等堿金屬離子進行了模擬比較,發(fā)現(xiàn)在阻礙構(gòu)象變化能力上KRbNa。3、對大于1M的不同濃度離子體系進行模擬,發(fā)現(xiàn)在3M濃度區(qū)間時有較穩(wěn)定的類A構(gòu)象的存在。而在較低鹽濃度溶液體系中,初始B構(gòu)象保持較穩(wěn)定狀態(tài),而A構(gòu)象向B構(gòu)象轉(zhuǎn)變,與實驗數(shù)據(jù)相吻合。對構(gòu)象進行分析發(fā)現(xiàn)Na+離子在DNA大溝的聚集可能是阻止構(gòu)象轉(zhuǎn)變的重要原因。這一研究豐富了人們對于DNA分子在鹽溶液下的構(gòu)象轉(zhuǎn)變的分子動力學(xué)模擬認識。然而需要注意當前分子動力學(xué)模擬的力場參數(shù)還尚未完善,表現(xiàn)在多種力場下的模擬最終構(gòu)象均非A構(gòu)象,部分DNA分子在模擬過程中出現(xiàn)堿基對分離等方面。
[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.
【學(xué)位授予單位】：山西師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O629.74
本文編號：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.
【學(xué)位授予單位】：山西師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O629.74
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1 鄭清川;蛋白質(zhì)結(jié)構(gòu)及分子對接的理論研究[D];吉林大學(xué);2006年
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