基于粗颗粒模型的细胞内大分子相互作用网络研究
发布时间：2018-11-12 21:07
【摘要】：细胞是生命的基本单位,对细胞的深入研究是揭开生命奥秘、征服疾病和造福人类的关键。细胞内含有蛋白质、核酸等生物大分子,这些大分子进行一系列复杂而又精密的生化反应和生理过程,形成了细胞内大分子相互作用网络。为了同步、直接的观察和研究这一作用网络,理论生物学家们构建了不同的虚拟细胞模型,但是有些模型太粗糙导致计算结果不准确,有些模型计算结果与实验接近,但计算量大计算耗时,无法推广应用到更深层次上的细胞研究中。 本论文在前人研究基础上,引入了静电作用和疏水作用项,构建了含206种最小蛋白质组的大肠杆菌粗颗粒细胞质模型和细胞模型,通过建立验证模型进行扩散运动分析,证明了构建的模型不仅计算量相对较小而且结果与前人实验和理论研究相近,能正确描述细胞内环境的运动性质,对于深入了解细胞内生理变化,进而探索生命奥秘具有非常重要的理论意义和现实意义。 本论文的主要研究内容和结果如下： 1.使用大肠杆菌最小蛋白质组的206种蛋白质构建细胞质粗颗粒模型,通过分析,发现不同pI值下206种蛋白质的种类数和总个数均呈双峰分布；而蛋白质在pH=7时的静电荷则与蛋白质的质量呈负的线性相关关系,即大部分带正电荷的蛋白质,其分子质量都比较小,而分子质量越大的蛋白质,可能带越多的负电荷。 2.基于郎之万方程,对构建的11个细胞质模型使用NAMD软件进行长时间尺度布朗动力学模拟,利用CHARMM、Mathematica和Python等程序编程辅助进行模拟结果的统计分析,结果发现细胞中蛋白质之间形成了复杂的相互作用网络关系。 3.研究正常浓度蛋白质组模型NMl-3、M8、M16的扩散运动和碰撞行为,进一步分析蛋白质相互作用网络的分布特征和规律,结果发现,蛋白质分子质量和电荷影响其扩散性质,蛋白质的扩散常数随荷质比增大而增大；细胞内蛋白质的平均碰撞数随绝对电荷的增大而增大,越接近电中性的蛋白质,其碰撞几率也越低。 4.分子之间直接或间接的接触会形成聚类,聚类的形状和大小反映了相互作用网络的空间分布,通过随机浓度蛋白质组模型RM1-6与正常浓度模型NM1-3对比,发现正常浓度模型的聚类平均值最大,细胞内蛋白质维持合适的浓度比例有利于形成稳定的聚类,随着时间变化,聚类的大小有轻微的波动,说明蛋白质作用网络处于一个动态平衡中。 5.在细胞质模型基础上引入RNA和环状DNA分子,构建大肠杆菌虚拟细胞模型,采用相同的模拟和分析方法,验证了蛋白质浓度及电荷对蛋白质在细胞内运动和相互作用的影响,该结论可以推广应用到整个细胞。 研究表明细胞中带正电荷蛋白质和带负电荷蛋白质维持合适的浓度比例有利于细胞内蛋白质作用网络的形成,蛋白质分子质量、电荷和浓度对这一作用网络有着非常重要的影响。
[Abstract]:Cell is the basic unit of life. The study of cell is the key to uncover the mystery of life, conquer disease and benefit mankind. The cells contain proteins nucleic acids and other biological macromolecules which carry out a series of complex and precise biochemical reactions and physiological processes which form a network of intracellular macromolecular interactions. In order to synchronize, observe and study this action network directly, theoretical biologists have constructed different virtual cell models, but some models are too rough to make the results inaccurate, and some models are close to the experimental results. However, the computation is time-consuming and cannot be applied to further cell research. In this paper, based on previous studies, electrostatic and hydrophobic interaction terms were introduced to construct the cytoplasmic model and cell model of E. coli coarse granules containing 206 minimum proteome. The diffusion motion analysis was carried out by establishing a validation model. It is proved that the proposed model not only has a relatively small amount of computation, but also has similar results to previous experiments and theoretical studies. It can accurately describe the motion properties of the intracellular environment, and is useful for further understanding of intracellular physiological changes. And then explore the mystery of life has very important theoretical and practical significance. The main contents and results of this thesis are as follows: 1. The coarse particle model of cytoplasm was constructed by using 206 proteins of the minimum proteome of Escherichia coli. It was found that the species number and the total number of 206 kinds of proteins under different pI values were distributed in two peaks. However, there is a negative linear correlation between the static charge of protein at pH= 7 and the mass of protein. That is, most positively charged proteins have smaller molecular weight, but the larger the molecular weight, the more negative charges may be. 2. Based on the Langzhiwan equation, the 11 cytoplasmic models were simulated with NAMD software for long time scale Brownian dynamics, and the statistical analysis of the simulation results was carried out with the aid of CHARMM,Mathematica and Python programs. The results showed that there were complex interaction networks between proteins in cells. 3. The diffusion motion and collision behavior of the proteome model NMl-3,M8,M16 with normal concentration were studied, and the distribution and regularity of protein interaction network were analyzed. The results showed that the molecular weight and charge of protein affected its diffusion properties. The diffusion constant of protein increases with the increase of the ratio of charge to mass. The average number of collisions increases with the increase of the absolute charge. The closer the protein is to the electrically neutral protein, the lower the collision probability is. 4. Direct or indirect contact between molecules forms clusters, and the shape and size of clusters reflect the spatial distribution of interaction networks. The random concentration proteome model (RM1-6) is compared with the normal concentration model (NM1-3). It was found that the average value of the normal concentration model was the largest, and the proper concentration ratio of intracellular protein was favorable to the formation of stable clustering, and the size of the cluster fluctuated slightly with the change of time. It shows that the protein action network is in a dynamic equilibrium. 5. The virtual cell model of Escherichia coli was constructed by introducing RNA and circular DNA molecules on the basis of cytoplasmic model. The same simulation and analysis methods were used to verify the effects of protein concentration and charge on the intracellular movement and interaction of proteins. This conclusion can be extended to the whole cell. It has been shown that the proper concentration of positively charged protein and negatively charged protein is beneficial to the formation of protein interaction network and the molecular weight of protein. Charge and concentration have a very important effect on this network.
【学位授予单位】：中央民族大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R329
本文编号：2328216
[Abstract]:Cell is the basic unit of life. The study of cell is the key to uncover the mystery of life, conquer disease and benefit mankind. The cells contain proteins nucleic acids and other biological macromolecules which carry out a series of complex and precise biochemical reactions and physiological processes which form a network of intracellular macromolecular interactions. In order to synchronize, observe and study this action network directly, theoretical biologists have constructed different virtual cell models, but some models are too rough to make the results inaccurate, and some models are close to the experimental results. However, the computation is time-consuming and cannot be applied to further cell research. In this paper, based on previous studies, electrostatic and hydrophobic interaction terms were introduced to construct the cytoplasmic model and cell model of E. coli coarse granules containing 206 minimum proteome. The diffusion motion analysis was carried out by establishing a validation model. It is proved that the proposed model not only has a relatively small amount of computation, but also has similar results to previous experiments and theoretical studies. It can accurately describe the motion properties of the intracellular environment, and is useful for further understanding of intracellular physiological changes. And then explore the mystery of life has very important theoretical and practical significance. The main contents and results of this thesis are as follows: 1. The coarse particle model of cytoplasm was constructed by using 206 proteins of the minimum proteome of Escherichia coli. It was found that the species number and the total number of 206 kinds of proteins under different pI values were distributed in two peaks. However, there is a negative linear correlation between the static charge of protein at pH= 7 and the mass of protein. That is, most positively charged proteins have smaller molecular weight, but the larger the molecular weight, the more negative charges may be. 2. Based on the Langzhiwan equation, the 11 cytoplasmic models were simulated with NAMD software for long time scale Brownian dynamics, and the statistical analysis of the simulation results was carried out with the aid of CHARMM,Mathematica and Python programs. The results showed that there were complex interaction networks between proteins in cells. 3. The diffusion motion and collision behavior of the proteome model NMl-3,M8,M16 with normal concentration were studied, and the distribution and regularity of protein interaction network were analyzed. The results showed that the molecular weight and charge of protein affected its diffusion properties. The diffusion constant of protein increases with the increase of the ratio of charge to mass. The average number of collisions increases with the increase of the absolute charge. The closer the protein is to the electrically neutral protein, the lower the collision probability is. 4. Direct or indirect contact between molecules forms clusters, and the shape and size of clusters reflect the spatial distribution of interaction networks. The random concentration proteome model (RM1-6) is compared with the normal concentration model (NM1-3). It was found that the average value of the normal concentration model was the largest, and the proper concentration ratio of intracellular protein was favorable to the formation of stable clustering, and the size of the cluster fluctuated slightly with the change of time. It shows that the protein action network is in a dynamic equilibrium. 5. The virtual cell model of Escherichia coli was constructed by introducing RNA and circular DNA molecules on the basis of cytoplasmic model. The same simulation and analysis methods were used to verify the effects of protein concentration and charge on the intracellular movement and interaction of proteins. This conclusion can be extended to the whole cell. It has been shown that the proper concentration of positively charged protein and negatively charged protein is beneficial to the formation of protein interaction network and the molecular weight of protein. Charge and concentration have a very important effect on this network.
【学位授予单位】：中央民族大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R329
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