臺灣博碩士論文加值系統

蛋白質功能與物理上的箝制會反映在序列的保留性上，在之前的研究中得知數種結構特徵例如：氨基酸堆疊密度、氨基算相對接觸面積以及結構動態與蛋白質序列變化擾動程度有一定的相關性。其中蛋白質加權連接數是一個簡單又強大的模型用以代表蛋白質氨基酸空間上的堆疊程度。但是單一一個氨基酸加權連接數模型的數值很難感覺到蛋白質氨基酸環境的擁擠程度。近期則有人提出利用沃羅諾依分割算法來劃分計算蛋白質中氨基酸的體積，並作為蛋白質結構的特徵。但是沃羅諾依切割出的體積往往在表面上會造成巨大的誤差數值。於是我們提出了“相對沃羅諾伊”體積比值模型。“相對沃羅諾伊”體積比值是基於沃羅諾伊鑲嵌法。 “相對沃羅諾伊”體積比是胺基酸自身的凡德瓦體積與其沃羅諾伊體積的比值，其數值介於0與1之間。利用這個特點可以量化出每個胺基酸的相對自由空間大小。更進一步則發現作為一個結構特徵，相對沃羅諾伊體積比與序列上胺基酸變化的擾動性有明顯的相關性。更進一步則發現其值與蛋白質結構上的動態資訊也有很高的相關性，無論是理論上計算的動態還是實驗測得的擾動。 總結來說”相對沃羅諾伊體積比”除了用以敘述蛋白質中胺基酸相對空間的環境，也可利用此結構特徵來研究蛋白質序列演化，結構以及動態關係。 

Functional and biophysical constraints of a protein cause different levels of residue conservation. In previous studies, structural properties such as packing density, relative solvent accessibility, and dynamics were found to be related to residue conservation derived from protein sequences. Weighted Contact Number (WCN) is a simple and powerful model to represent packing density, but it’s hard to feel how a residue so crowded by single value. Recently, The Voronoi volume has emerged as a new structural property to reflect residue conservation. However, residues near protein surface often have an enormous Voronoi Volume and make the estimation of evolutionary constraints difficult. Therefore, we present a new model to describe residue packing density: relative space of Voronoi volume (RSV). Relative Space of Voronoi volume (RSV) is based on the Voronoi tessellation method. RSV ranges from 0 to 1 and is defined as the ratio calculated by Voronoi volume subtracting van der Waals volume divided by Voronoi volume of a target residue. It can quantify the level of available space for every residue. We found RSV correlates significantly with the protein evolutionary rate with a correlation coefficient more than 0.5 between RSV and conservation profiles. Moreover, RSV is also related to local protein mobility which is quantified by theoretical or experimental methods. RSV not only describes structural constraints of buried but surface residues properly. To sum up, RSV turns Voronoi volume into a ratio and it could become a promising and practical structural determinant to study protein sequence, structure, and dynamic relationships in the future

Contents:

1 Introduction 1
1.1 The relationship between protein structure and dynamic properties 1
1.2 The relationship between protein structure and site-specific properties 2
1.3 The relationship between protein dynamics and site-specific properties 2
1.4 A new model from Voronoi tessellations 3
2 Methods 5
2.1 Residue Voronoi volume (VO) 5
2.2 Weighted Contact Number(WCN) 5
2.3 Relative space of Voronoi volume (RSV) 6
2.4 Relative solvent accessibility (RSA) 6
2.5 Sequence conservation 7
2.6 Theoretical and experimental dynamic properties 7
2.7 Processing data noises 9
2.8 Profile Comparison 10
2.9 Dataset 10
3 Results 11
3.1 Comparison between RSV and VO. 11
3.2 Comparison between RSV and Structural properties, Weighted Contact Number and Relative Solvent Accessibility. 11
3.3 Comparison between RSV and Dynamic Properties, The Experimental thermal fluctuations and Theoretical thermal fluctuations from Coarse Grained network model. 12
3.4 Comparison between RSV and conservation profiles 13
4 Discussion and Conclusions 16
4.1 RSV is more matching with other properties than VO 16
4.2 RSV is more quantifiable than Weighted Contact Numbers and RSA. 16
4.3 RSV is a stable ratio 17
4.4 Conclusion 18
5 List of abbreviations used 19
6 References 20
7 Tables: 27
Table 1. 27
Table 2. 28
Table 3. 29
8 Figures 30
Figure 1. 30
Figure 2. 31
Figure 3. 32
Figure 4. 33
Figure 5. 34
Figure 6. 35
Figure 7. 36
Figure 8. 37
Figure 9. 38
Figure 11. 40
Figure 12. 41
Figure 13. 42
Figure 14. 43
Figure 15. 44
Figure 16. 45
Figure 17. 46
Figure 18. 47
Figure 19. 48
Figure 20. 49
Figure 21. 50
Figure 22. 51

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