以生物資訊法研究穩定Asparagine在左手螺旋形下的交互作用力; An Analysis of the Stabilizing Energies for the Partially Allowed Left-Handed Alphaical Conformations of Asparagine

Please use this identifier to cite or link to this item: http://ir.lib.ncu.edu.tw/handle/987654321/6357

Title:	以生物資訊法研究穩定Asparagine在左手螺旋形下的交互作用力;An Analysis of the Stabilizing Energies for the Partially Allowed Left-Handed Alphaical Conformations of Asparagine
Authors:	李中饋;Chung-Kuei Lee
Contributors:	化學研究所
Keywords:	生物資訊;Ramachandran plot;Left-handed alpha-helix
Date:	2007-07-05
Issue Date:	2009-09-22 10:18:09 (UTC+8)
Publisher:	國立中央大學圖書館
Abstract:	本篇研究整體性地分析Protein Data Bank(PDB)中2,058個X-ray解析度優於2.0 Å的non-homologous蛋白質結構，並進行不同主鏈構形區域propensity的分析，發現 Asparagine(Asn) 和一些極性胺基酸於左手螺旋構形(alpha-L)有相當高的分佈趨勢，但是Asn 的propensity是最高的，這種趨勢於過去文獻中也曾被報導過，但是其原因並不清楚。因此本論文使用了生物資訊法及量子化學計算分析蛋白質結構中常見的作用力，如氫鍵、溶合作用及偶極-偶極作用力(dipole-dipole interaction)，研究是否是造成 Asn 在較高能量 alpha-L 構形的高度分佈的原因。根據Asn及其他極性胺基酸於不同主鏈構形下的分析，顯示氫鍵對於 Asn 在 alpha-L 構形的分佈沒有特殊貢獻；量子化學計算分析溶合作用發現，不同極性的溶劑可以穩定 Asn 的 alpha-L 構形，從蛋白質資料庫分析也發現 alpha-L 構形的Asn 具有相當高的SASA (較高的溶合能)，然而其溶合能強度較難精確估算，難以進一步瞭解溶合作用的強度；此外，氣態量子化學計算顯示，Asn較Ala在 alpha-L構形下有較高的分佈，暗示其 alpha-L構形的穩定性與其獨特的側鏈化學性質有關。進一步分析 Asn 主鏈carbonyl group和其側鏈carbonyl group 的偶極-偶極交互作用力，顯示此作用力可以有效穩定 alpha-L 構形，但是由於右手螺旋構形 (alpha-R) 及左手螺旋構形 (alpha-L) 互為鏡像，所以此一交互作用力對 alpha-R 構形則有去穩定化的作用，而此一結果，造成 Asn 的 alpha-L 和 alpha-R 構形能量差距的減少，導致 Asn 在 alpha-L 構形分佈趨勢較其它胺基酸高出許多。因此從上述分析，歸納出 Asn 主鏈及側鏈carbonyl group之間的作用及水溶液的溶合作用，為造成 Asn 於 alpha-L 有高度分佈的主要原因。 In this study, a systemic analysis of the new protein database was performed. A dataset of 2,058 non-homogenous protein structures with resolutions of x-ray diffraction better than 2.0 Å were extracted from the currently released protein data bank (PDB). The propensities of 19 non-glycl amino acids at different main-chain conformations were calculated. The results show that the asparagine (Asn) as well as some polar amino acids prefers to occur at the higher energy alpha-L conformation. In particular, the Asn has the highest propensity. The result was reported in the previous literatures based on the analysis of fewer protein structures. However, the reasons which lead to such result are not clear. This study employed the bioinformatics analysis and quantum chemical calculations to study the roles of some important interactions such as hydrogen-bonding, solvation energy, and dipole-dipole interactions in stabilizing the Asn at alpha-L conformation. The results show that hydrogen-bond percentage of Asn at alpha-L conformation is lower than that at alpha-R and beta-conformations indicating the hydrogen bonding is not the major stabilizing energy source. The solvation energies estimated from the B3LYP/6-31G(d,p) level with polarizable continuum (PCM) solvation models show the solvents with different polarities can stabilize the Asn at alpha-L conformation. The database analysis also shows similar results where the Asn at alpha-L conformation has higher solvent accessible surface area (SASA) than that at other conformations. However, due to the complicated environments of Asn in protein matrix, the strength of the solvation can not be calculated accurately. More interestingly, the gas phase quantum chemical calculations show the populations of Asn at alpha-L conformation is higher than Ala at alpha-L conformation. The results of these “environment free” calculations hint for that the Asn can stabilize itself with alpha-L conformation, may arise from its unique side chain. Further analysis shows that the carbonyl-carbonyl dipole-dipole interactions of the Asn main chain and side chain can stabilize the alpha-L conformation. In contrast, such interaction can destabilize the alpha-R conformation due to the fact of alpha-L and alpha-R conformations being mirror images. This interaction stabilizes the alpha-L conformation, at the same time, destabilizes the alpha-R conformation, decreasing their energy difference and resulting in the highest propensity of Asn at alpha-L conformation. In conclusion, Asn at alpha-L conformation can be stabilized by the solution. Additionally, the propensity of Asn at alpha-L conformation is enhanced by the carbonyl dipole-dipole interactions of main and side chains.
Appears in Collections:	[Graduate Institute of Chemistry] Electronic Thesis & Dissertation

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