DNA構(gòu)象在鹽溶液中的動(dòng)力學(xué)模擬轉(zhuǎn)變研究
發(fā)布時(shí)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(dòng)中扮演著至關(guān)重要的作用,是動(dòng)植物細(xì)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(xì)胞內(nèi)的結(jié)構(gòu)是動(dòng)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(dāng)前構(gòu)象下的微擾動(dòng),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(shí)還受到溶液條件的影響。由于在DNA的復(fù)制、轉(zhuǎn)錄、翻譯過(guò)程中通常會(huì)有規(guī)則性的構(gòu)象變化發(fā)生,研究者認(rèn)為DNA是通過(guò)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(jì)納米尺度結(jié)構(gòu),由于通過(guò)其適當(dāng)?shù)男蛄信帕锌梢允笵NA列折疊成定義明確的二級(jí)結(jié)構(gòu),DNA被認(rèn)為有望發(fā)展為納米儀器的移動(dòng)部件,如納米鉗子。并可以通過(guò)DNA不同的構(gòu)象之間的轉(zhuǎn)換來(lái)驅(qū)動(dòng)基于DNA的可控分子機(jī)械。因此人們對(duì)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?xiàng)l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(rèn)為不僅在基因的表達(dá)中起著重要作用,同時(shí)也在某些蛋白質(zhì)-DNA復(fù)合物中作為識(shí)別基序,DNA的A/B構(gòu)象相互轉(zhuǎn)變過(guò)程被認(rèn)為是蛋白-DNA復(fù)合識(shí)別的模式之一,同時(shí)也被認(rèn)為是推動(dòng)DNA進(jìn)行自組裝,以及通過(guò)病毒蛋白殼體的主要推動(dòng)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。現(xiàn)有的研究表明,溶液中的堿金屬平衡離子會(huì)對(duì)DNA的A→B構(gòu)象轉(zhuǎn)變過(guò)程起到一個(gè)阻礙的作用。且在實(shí)驗(yàn)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(guò)模擬得到高濃度鹽溶液中初始A-DNA構(gòu)型隨時(shí)間保持構(gòu)型穩(wěn)定的結(jié)果。本文基于分子動(dòng)力學(xué)原理,選用GROMACS5.1.4軟件包,對(duì)標(biāo)準(zhǔn)構(gòu)型的A-DNA和B-DNA在高濃度鹽溶液中的構(gòu)象變化進(jìn)行模擬分析。進(jìn)行了以下研究:1、對(duì)當(dāng)今各種分子動(dòng)力學(xué)模擬力場(chǎng)進(jìn)行比較,得出了Charmm36力場(chǎng)最為適用于這一體系。2、對(duì)Na、K、Rb等堿金屬離子進(jìn)行了模擬比較,發(fā)現(xiàn)在阻礙構(gòu)象變化能力上KRbNa。3、對(duì)大于1M的不同濃度離子體系進(jìn)行模擬,發(fā)現(xiàn)在3M濃度區(qū)間時(shí)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(shí)驗(yàn)數(shù)據(jù)相吻合。對(duì)構(gòu)象進(jìn)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(duì)于DNA分子在鹽溶液下的構(gòu)象轉(zhuǎn)變的分子動(dòng)力學(xué)模擬認(rèn)識(shí)。然而需要注意當(dāng)前分子動(dòng)力學(xué)模擬的力場(chǎng)參數(shù)還尚未完善,表現(xiàn)在多種力場(chǎng)下的模擬最終構(gòu)象均非A構(gòu)象,部分DNA分子在模擬過(guò)程中出現(xiàn)堿基對(duì)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(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O629.74
本文編號(hào)：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(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O629.74
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1 歐陽(yáng)芳平 ,徐慧 ,郭愛(ài)敏 ,李燕峰;分子模擬方法及其在分子生物學(xué)中的應(yīng)用[J];生物信息學(xué);2005年01期
相關(guān)博士學(xué)位論文 前1條
1 鄭清川;蛋白質(zhì)結(jié)構(gòu)及分子對(duì)接的理論研究[D];吉林大學(xué);2006年
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