【摘要】：高分辨冷凍電子顯微學(xué)重構(gòu)病毒需要大量（顆粒數(shù)以萬(wàn)計(jì)）冷凍電鏡照片，程序處理這些電鏡照片耗費(fèi)大量時(shí)間。處理數(shù)據(jù)的過(guò)程中篩選顆粒的方法以及噪聲等因素的影響，實(shí)際上程序處理的顆粒中有部分顆粒是噪聲粒子。在重構(gòu)中程序處理的批量數(shù)據(jù)中包含了這些顆粒，顆粒數(shù)的增加反映在程序計(jì)算用時(shí)上是成指數(shù)增長(zhǎng)。在精修的過(guò)程中，相位殘差與顆粒數(shù)呈現(xiàn)出雙高斯峰模型。顯然，應(yīng)用統(tǒng)計(jì)學(xué)以及重構(gòu)方法的原因，相位殘差和顆粒數(shù)圖顯示分屬于兩個(gè)高斯峰，這些主峰粒子與側(cè)峰粒子是屬于兩類粒子。本文詳細(xì)闡述了二十面體病毒三維重構(gòu)技術(shù)的原理、方法和三維重構(gòu)數(shù)據(jù)處理流程、算法。通過(guò)分析處理顆粒在程序處理數(shù)據(jù)過(guò)程中的變化特點(diǎn)，來(lái)了解相位殘差顆粒數(shù)的混合高斯模型；本文還重構(gòu)了腺病毒Ad5F35的衣殼結(jié)構(gòu)，揭示了纖維penton base結(jié)合守恒，洞悉了纖維與受體之間的相互作用。其具體內(nèi)容如下： 我們重構(gòu)了Ad5F35衣殼的三維結(jié)構(gòu)表明腺病毒的纖維penton base結(jié)合是守恒的。通過(guò)比較Ad5F35密度圖的纖維結(jié)構(gòu)和由c終端knob和shaft區(qū)組成的虛擬同源Ad35模型的纖維結(jié)構(gòu)，我們證實(shí)了纖尾的c終端部分（殘留22 43）就是shaft長(zhǎng)度的一部分，它位于纖維shaft的主干底部。此外基于我們的Ad5F35結(jié)構(gòu)，即CD46和整合素受體與Ad5F35衣殼的相互作用模型，表明短纖維的Ads可能能夠同時(shí)綁定受體整合素和CD46。通過(guò)處理多套已經(jīng)發(fā)表在國(guó)際相關(guān)領(lǐng)域的核心期刊上的各類病毒數(shù)據(jù)，來(lái)研究混合高斯模型中兩峰間距和病毒結(jié)構(gòu)分辨率的對(duì)應(yīng)關(guān)系。用多組數(shù)據(jù)在不同傅里葉半徑下精修，對(duì)比分析在相同半徑下每輪精修后的結(jié)果：對(duì)于主峰顆粒，在同一傅里葉半徑下，精修次數(shù)越多，峰值的位置不變，但是整個(gè)峰值顆粒越來(lái)越集中在峰值附近；精修次數(shù)增加，顆粒的分布幾率越來(lái)越趨向于峰值附近，，應(yīng)該是測(cè)量（精修）越來(lái)越精確的反映。對(duì)主峰顆粒，在某同一半徑下從剛開(kāi)始精修的時(shí)候到終極精修的各輪數(shù)據(jù)進(jìn)行分析，看是否有小側(cè)峰出現(xiàn)，觀察側(cè)峰的變化趨勢(shì)。側(cè)峰的顆粒也進(jìn)行上述實(shí)驗(yàn)。在多組數(shù)據(jù)在不同傅里葉半徑下精修重構(gòu)，對(duì)比分析不同傅里葉半徑下終極精修后的結(jié)果，主峰顆粒，精修傅里葉半徑增加，峰值的位置向右平移并且精修次數(shù)越多。
[Abstract]:High resolution frozen electron microscopy (HREM) reconstruction of viruses requires a large number of (tens of thousands of particles) of frozen electron microscopy photographs, and the processing of these electron microscopic photographs by program takes a lot of time. In fact, some of the particles processed by the program are noise particles. These particles are included in the batch data processed by the program during the reconfiguration, and the increase in the number of particles is reflected in the exponential increase in the calculation time of the program. In the process of refinement, the phase residuals and the number of particles show a double Gao Si peak model. Obviously, for the reasons of applying statistics and reconstruction method, the phase residuals and particle number graphs belong to two Gao Si peaks, and these main peak particles and side peak particles belong to two kinds of particles. In this paper, the principle, method, data processing flow and algorithm of three dimensional reconstruction of icosahedron virus are described in detail. The mixed Gao Si model of the number of phase residuals is obtained by analyzing the changing characteristics of the processed particles in the process of data processing, and the capsid structure of the adenovirus Ad5F35 is reconstructed, which reveals the conserved binding of fiber penton base. The interaction between fibers and receptors is well understood. The main contents are as follows: we reconstruct the three-dimensional structure of Ad5F35 capsid and show that the penton base binding of adenovirus fibers is conserved. By comparing the fiber structure of the Ad5F35 density map with the fiber structure of the virtual homologous Ad35 model composed of c terminal knob and shaft region, we confirm that the c terminal part of the tail (residual 22 / 43) is part of the length of shaft. It is located at the trunk bottom of the fiber shaft. In addition, based on our Ad5F35 structure, that is, the interaction model between CD46 and integrin receptor and Ad5F35 capsid, it is suggested that the Ads of short fiber may be able to bind integrin and CD46. at the same time. The relationship between the distance between two peaks and the resolution of virus structure in mixed Gao Si model is studied by processing several sets of virus data published in core journals of international related fields. Using multiple sets of data at different Fourier radii, the results of each round refinement at the same radius are compared and analyzed: for the main peak particles, the more refined the number of refinements in the same Fourier radius, the constant the position of the peak value. However, the whole peak particle is more and more concentrated near the peak value, and the distribution probability of the particle is more and more close to the peak value with the increase of refinement times, which should be more and more accurate reflection of measurement (refinement). The data of each round of the main peak particle from the beginning of finishing to the final refinement at the same radius are analyzed to see if there is a small side peak and observe the change trend of the side peak. The above experiments were also carried out on the side peak particles. After several sets of data are refined and reconstructed under different Fourier radii, the results of the final refinement under different Fourier radii are compared and analyzed. The main peak particles, the refined Fourier radius are increased, the peak position is shifted to the right and the number of refinements is increased.
【學(xué)位授予單位】：湘潭大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R373

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 張運(yùn)楚;李貽斌;張建濱;;高斯混合背景模型的方差估計(jì)研究[J];計(jì)算機(jī)工程與應(yīng)用;2012年04期

本文編號(hào)：2274264