博碩士論文 942203060 詳細資訊




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姓名 李中饋(Chung-Kuei Lee)  查詢紙本館藏   畢業系所 化學學系
論文名稱 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)
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摘要(中) 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。
摘要(英) 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.
關鍵字(中) ★ 生物資訊 關鍵字(英) ★ Ramachandran plot
★ Left-handed alpha-helix
論文目次 中文摘要 i
Abstract ii
誌謝 ………………………………………...………………………………..iii
總目錄 ………………………………………………………………………….iv
圖目錄 ………………………………………………………………………….vi
表目錄 ………………………………………………………………………….ix
第一章 導論 1
1-1 蛋白質結構分析背景簡介 1
1-2 蛋白質結構 3
1-2-1 胺基酸 3
1-2-2 胺基酸序列及結構表示 6
1-2-3 蛋白質結構組織 9
1-2-3-1 二級結構-螺旋狀結構(a helice) 11
1-2-3-2 二級結構-平板狀構形(b sheet) 13
1-3 蛋白質結構來源 16
1-4 蛋白質結構資料庫(PDB) 16
1-5 蛋白質主鏈構形分析方法(Ramachandran plot) 17
1-6 Disallowed region的結構分析 20
1-7 不同胺基酸對結構偏好 23
1-8 研究動機 26
第二章 計算及分析方法 27
2-1 資料庫之建立 27
2-2 Ramachandran plot之建立及統計資料篩選 29
2-3 Propensity的計算 29
2-4 氫鍵結構資料分析 31
2-5 偶極-偶極作用力(dipole-dipole interaction)分析 32
2-6 Solvent accessible surface area(SASA)計算 32
2-7 量子計算方法 33
2-8 側鏈構形的定義 34
2-9 蛋白質資訊分析程式: Pine (Protein INformation Extraction) 35
第三章 結果 38
3-1 Non-Glycl Ramachandran Plot 38
3-2 a-L 區域中胺基酸的propensity 42
3-3 a-R、b
參考文獻 (1) Anfinsen, C. B., Principles that govern the folding of protein chains. Science 1973, 181, (96), 223-30.
(2) Anfinsen, C. B.; Haber, E.; Sela, M.; White, F. H., Jr., The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain. Proc Natl Acad Sci U S A 1961, 47, 1309-14.
(3) Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; IShindyalov, I. N.; Bourne, P. E., The Protein Data Bank. Nucleic Acids Research 2000, 28, 235-242.
(4) Murzin, A. G.; Brenner, S. E.; Hubbard, T.; Chothia, C., Scop - a Structural Classification of Proteins Database for the Investigation of Sequences and Structures. Journal of Molecular Biology 1995, 247, (4), 536-540.
(5) Pauling, L.; Corey, R. B.; Branson, H. R., The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. Proc Natl Acad Sci U S A 1951, 37, (4), 205-11.
(6) Pauling, L.; Corey, R. B., The pleated sheet, a new layer configuration of polypeptide chains. Proc Natl Acad Sci U S A 1951, 37, (5), 251-6.
(7) Frishman, D.; Argos, P., Knowledge-based protein secondary structure assignment. Proteins-Structure Function and Genetics 1995, 23, (4), 566-579.
(8) Kabsch, W.; Sander, C., Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 1983, 22, (12), 2577-637.
(9) Ramachandran, G. N.; Ramakrishnan, C.; Sasisekharan, V., Stereochemistry of polypeptide chain configurations. J. Mol. Biol. 1963, 7, 95-99.
(10) Ramachandran, G. N.; Sasisekharan, V., Conformation of polypeptides and proteins. Advanced Proteins Chemistry 1968, 23, 283-437.
(11) Ramachandran, G. N.; Venkatachalam, C. M.; Krimm, S., Stereochemical criteria for polypeptide and protein chain conformations. 3. Helical and hydrogen-bonded polypeptide chains. Biophys J 1966, 6, (6), 849-72.
(12) Ramakrishnan, C.; Srinivasan, N., Glycyl Residues in Proteins and Peptides - an Analysis. Current Science 1990, 59, (17-18), 851-861.
(13) Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M., PRO-CHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystallallogr. 1993, 26, 283-291.
(14) Hooft, R. W. W.; Vriend, G.; Sander, C.; Abola, E. E., Errors in protein structures. Nature 1996, 381, (6580), 272-272.
(15) Kleywegt, G. J.; Jones, T. A., Phi/psi-chology: Ramachandran revisited. Structure 1996, 4, (12), 1395-400.
(16) Gunasekaran, K.; Ramakrishnan, C.; Balaram, P., Disallowed Ramachandran conformations of amino acid residues in protein structures. Journal of Molecular Biology 1996, 264, (1), 191-198.
(17) Pal, D.; Chakrabarti, P., On residues in the disallowed region of the Ramachandran map. Biopolymers 2002, 63, (3), 195-206.
(18) Aurora, R.; Rose, G. D., Helix capping. Protein Science 1998, 7, (1), 21-38.
(19) Lifson, S.; Sander, C., Antiparallel and parallel beta-strands differ in amino acid residue preferences. Nature 1979, 282, (5734), 109-11.
(20) Schimmel, P. R.; Flory, P. J., Conformational energies and configurational statistics of copolypeptides containing L-proline. J Mol Biol 1968, 34, (1), 105-20.
(21) Summers, N. L.; Karplus, M., Modeling of Globular-Proteins - a Distance-Based Data Search Procedure for the Construction of Insertion Deletion Regions and Pro Reversible Non-Pro Mutations. Journal of Molecular Biology 1990, 216, (4), 991-1016.
(22) Maigret, B.; Perahia, D.; Pullman, B., Molecular orbital calculations on the conformation of polypeptides and proteins. IV. The conformation of the prolyl and hydroxyprolyl residues. J Theor Biol 1970, 29, (2), 275-91.
(23) Radzicka, A.; Pedersen, L.; Wolfenden, R., Influences of solvent water on protein folding: free energies of solvation of cis and trans peptides are nearly identical. Biochemistry 1988, 27, (12), 4538-41.
(24) Srinivasan, N.; Anuradha, V. S.; Ramakrishnan, C.; Sowdhamini, R.; Balaram, P., Conformational Characteristics of Asparaginyl Residues in Proteins. International Journal of Peptide and Protein Research 1994, 44, (2), 112-122.
(25) Allen, F. H.; Baalham, C. A.; Lommerse, J. P. M.; Raithby, P. R., Carbonyl-carbonyl interactions can be competitive with hydrogen bonds. Acta Crystallographica Section B-Structural Science 1998, 54, 320-329.
(26) Deane, C. M.; Allen, F. H.; Taylor, R.; Blundell, T. L., Carbonyl-carbonyl interactions stabilize the partially allowed Ramachandran conformations of asparagine and aspartic acid. Protein Engineering 1999, 12, (12), 1025-1028.
(27) Wang, G. L.; Dunbrack, R. L., PISCES: recent improvements to a PDB sequence culling server. Nucleic Acids Research 2005, 33, W94-W98.
(28) Kleywegt, G. J.; Henrick, K.; Dodson, E. J.; van Aalten, D. M. F., Pound-wise but penny-foolish: How well do micromolecules fare in macromolecular refinement? Structure 2003, 11, (9), 1051-1059.
(29) Lovell, S. C.; Word, J. M.; Richardson, J. S.; Richardson, D. C., Asparagine and glutamine rotamers: B-factor cutoff and correction of amide flips yield distinct clustering. Proceedings of the National Academy of Sciences of the United States of America 1999, 96, (2), 400-405.
(30) Word, J. M.; Lovell, S. C.; LaBean, T. H.; Taylor, H. C.; Zalis, M. E.; Presley, B. K.; Richardson, J. S.; Richardson, D. C., Visualizing and quantifying molecular goodness-of-fit: Small-probe contact dots with explicit hydrogen atoms. Journal of Molecular Biology 1999, 285, (4), 1711-1733.
(31) Anderson, R. J.; Weng, Z. P.; Campbell, R. K.; Jiang, X. L., Main-chain conformational tendencies of amino acids. Proteins-Structure Function and Bioinformatics 2005, 60, (4), 679-689.
(32) Joughin, B. A.; Yaffe, M. B.; Tidor, B., Computational prediction of protein phosphopeptide-binding sites. Protein Science 2004, 13, 146-146.
(33) Eswar, N.; Ramakrishnan, C., Deterministic features of side-chain main-chain hydrogen bonds in globular protein structures. Protein Engineering 2000, 13, (4), 227-238.
(34) MacKerell, A. D.; Bashford, D.; Bellott, M.; Dunbrack, R. L.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher, W. E.; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M., All-atom empirical potential for molecular modeling and dynamics studies of proteins. Journal of Physical Chemistry B 1998, 102, (18), 3586-3616.
(35) Arridge, R. G. C.; Cannon, C. G., Calculation of The CONH dipole contribution to lattice energies of amines, polyamides, and polypeptides. Proc. Roy. Soc. A. 1964, 278, 91-109.
(36) Cavallo, L.; Kleinjung, J.; Fraternali, F., POPS: a fast algorithm for solvent accessible surface areas at atomic and residue level. Nucleic Acids Research 2003, 31, (13), 3364-3366.
(37) Hasel, W.; Hendrikson, T. F.; Stil, W. C., A rapid approximation to the solvent accessible areas of atoms. Tetrahedron Comput Methodol 1988, 1, 103-116.
(38) M. J. Frisch, G. W. T., H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, and J. A. Pople Gaussian 03 (Revision B02), Gaussian, Inc.: Pittsburgh PA, 2003.
(39) Becke, A. D., Density-Functional Thermochemistry. III. The Role of Exact Exchange. J. Chem. Phys. 1993, 98, 5648.
(40) Lee, C.; Yang, W.; Parr, R. G., Development of the Colle-Salvetti Correlation-Energy Formula Into a Functional of the Electron Density. Physical Review B 1988, 37, 785.
(41) Petersson, G. A.; Al-Laham, M. A., A Complete Basis Set Model Chemistry. II. Open-Shell Systems and the Total Energies of the First-Row Atoms. J. Chem. Phys. 1991, 94, 6081.
(42) Cossi, M.; Barone, V., Time-dependent density functional theory for molecules in liquid solutions. Journal of Chemical Physics 2001, 115, (10), 4708-4717.
(43) Lovell, S. C.; Davis, I. W.; Adrendall, W. B.; de Bakker, P. I. W.; Word, J. M.; Prisant, M. G.; Richardson, J. S.; Richardson, D. C., Structure validation by C alpha geometry: phi,psi and C beta deviation. Proteins-Structure Function and Genetics 2003, 50, (3), 437-450.
(44) Chou, P. Y.; Fasman, G. D., Conformational parameters for amino acids in helical, beta-sheet, and random coil regions calculated from proteins. Biochemistry 1974, 13, (2), 211-22.
(45) Paulini, R.; Muller, K.; Diederich, F., Orthogonal multipolar interactions in structural chemistry and biology. Angew Chem Int Ed Engl 2005, 44, (12), 1788-805.
(46) Schweizer, E.; Hoffmann-Roder, A.; Olsen, J. A.; Seiler, P.; Obst-Sander, U.; Wagner, B.; Kansy, M.; Banner, D. W.; Diederich, F., Multipolar interactions in the D pocket of thrombin: large differences between tricyclic imide and lactam inhibitors. Org Biomol Chem 2006, 4, (12), 2364-75.
(47) Olsen, J. A.; Banner, D. W.; Seiler, P.; Obst Sander, U.; D'Arcy, A.; Stihle, M.; Muller, K.; Diederich, F., A fluorine scan of thrombin inhibitors to map the fluorophilicity/fluorophobicity of an enzyme active site: evidence for C-F...C=O interactions. Angew Chem Int Ed Engl 2003, 42, (22), 2507-11.
(48) Hayes, I. C.; Stone, A. J., J. Mol. Phys. 1984, 53, 83-105.
(49) Maccallum, P. H.; Poet, R.; Milner-White, E. J., Coulombic attractions between partially charged main-chain atoms stabilise the right-handed twist found in most beta-strands. J Mol Biol 1995, 248, (2), 374-84.
(50) Maccallum, P. H.; Poet, R.; Milner-White, E. J., Coulombic interactions between partially charged main-chain atoms not hydrogen-bonded to each other influence the conformations of alpha-helices and antiparallel beta-sheet. A new method for analysing the forces between hydrogen bonding groups in proteins includes all the Coulombic interactions. J Mol Biol 1995, 248, (2), 361-73.
(51) http://www.chemistrydaily.com/chemistry/Amino_acid
(52) http://matcmadison.edu/biotech/resources/proteins/labManual/
chapter_2.htm
(53)Voet/Biochemistry 1990 John Wiley
.
(54)http://employees.csbsju.edu/hjakubowski/classes/ch331/protstruc ture/
olunderstandconfo.html
(55)http://www.biochem.ucl.ac.uk/~roman/procheck/manual/examples/
plot_01.html]
指導教授 蔡惠旭(Hui-Hsu Tsai) 審核日期 2007-7-23
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