基于粗顆粒模型的細胞內(nèi)大分子相互作用網(wǎng)絡研究
發(fā)布時間：2018-11-12 21:07
【摘要】：細胞是生命的基本單位,對細胞的深入研究是揭開生命奧秘、征服疾病和造福人類的關鍵。細胞內(nèi)含有蛋白質(zhì)、核酸等生物大分子,這些大分子進行一系列復雜而又精密的生化反應和生理過程,形成了細胞內(nèi)大分子相互作用網(wǎng)絡。為了同步、直接的觀察和研究這一作用網(wǎng)絡,理論生物學家們構建了不同的虛擬細胞模型,但是有些模型太粗糙導致計算結果不準確,有些模型計算結果與實驗接近,但計算量大計算耗時,無法推廣應用到更深層次上的細胞研究中。 本論文在前人研究基礎上,引入了靜電作用和疏水作用項,構建了含206種最小蛋白質(zhì)組的大腸桿菌粗顆粒細胞質(zhì)模型和細胞模型,通過建立驗證模型進行擴散運動分析,證明了構建的模型不僅計算量相對較小而且結果與前人實驗和理論研究相近,能正確描述細胞內(nèi)環(huán)境的運動性質(zhì),對于深入了解細胞內(nèi)生理變化,進而探索生命奧秘具有非常重要的理論意義和現(xiàn)實意義。 本論文的主要研究內(nèi)容和結果如下： 1.使用大腸桿菌最小蛋白質(zhì)組的206種蛋白質(zhì)構建細胞質(zhì)粗顆粒模型,通過分析,發(fā)現(xiàn)不同pI值下206種蛋白質(zhì)的種類數(shù)和總個數(shù)均呈雙峰分布；而蛋白質(zhì)在pH=7時的靜電荷則與蛋白質(zhì)的質(zhì)量呈負的線性相關關系,即大部分帶正電荷的蛋白質(zhì),其分子質(zhì)量都比較小,而分子質(zhì)量越大的蛋白質(zhì),可能帶越多的負電荷。 2.基于郎之萬方程,對構建的11個細胞質(zhì)模型使用NAMD軟件進行長時間尺度布朗動力學模擬,利用CHARMM、Mathematica和Python等程序編程輔助進行模擬結果的統(tǒng)計分析,結果發(fā)現(xiàn)細胞中蛋白質(zhì)之間形成了復雜的相互作用網(wǎng)絡關系。 3.研究正常濃度蛋白質(zhì)組模型NMl-3、M8、M16的擴散運動和碰撞行為,進一步分析蛋白質(zhì)相互作用網(wǎng)絡的分布特征和規(guī)律,結果發(fā)現(xiàn),蛋白質(zhì)分子質(zhì)量和電荷影響其擴散性質(zhì),蛋白質(zhì)的擴散常數(shù)隨荷質(zhì)比增大而增大；細胞內(nèi)蛋白質(zhì)的平均碰撞數(shù)隨絕對電荷的增大而增大,越接近電中性的蛋白質(zhì),其碰撞幾率也越低。 4.分子之間直接或間接的接觸會形成聚類,聚類的形狀和大小反映了相互作用網(wǎng)絡的空間分布,通過隨機濃度蛋白質(zhì)組模型RM1-6與正常濃度模型NM1-3對比,發(fā)現(xiàn)正常濃度模型的聚類平均值最大,細胞內(nèi)蛋白質(zhì)維持合適的濃度比例有利于形成穩(wěn)定的聚類,隨著時間變化,聚類的大小有輕微的波動,說明蛋白質(zhì)作用網(wǎng)絡處于一個動態(tài)平衡中。 5.在細胞質(zhì)模型基礎上引入RNA和環(huán)狀DNA分子,構建大腸桿菌虛擬細胞模型,采用相同的模擬和分析方法,驗證了蛋白質(zhì)濃度及電荷對蛋白質(zhì)在細胞內(nèi)運動和相互作用的影響,該結論可以推廣應用到整個細胞。 研究表明細胞中帶正電荷蛋白質(zhì)和帶負電荷蛋白質(zhì)維持合適的濃度比例有利于細胞內(nèi)蛋白質(zhì)作用網(wǎng)絡的形成,蛋白質(zhì)分子質(zhì)量、電荷和濃度對這一作用網(wǎng)絡有著非常重要的影響。
[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.
【學位授予單位】：中央民族大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R329
本文編號：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.
【學位授予單位】：中央民族大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R329
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