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博碩士論文 etd-0828107-231150 詳細資訊
Title page for etd-0828107-231150
論文名稱
Title
利用α碳原子座標重建蛋白質骨架結構之方法
Reconstruction of Protein Backbone with the α-arbon Coordinates
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
56
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2007-07-05
繳交日期
Date of Submission
2007-08-28
關鍵字
Keywords
α碳原子、重建、骨架、蛋白質
backbone, reconstruction, α-carbon, protein
統計
Statistics
本論文已被瀏覽 5702 次,被下載 1914
The thesis/dissertation has been browsed 5702 times, has been downloaded 1914 times.
中文摘要
利用α碳原子座標重建蛋白質骨架結構之方法
由一個已知α碳原子3D 座標的胺基酸序列,建構出完整包含所有原子(氮、碳及氧原子)的蛋白質骨架,即為所謂的全原子蛋白質骨架重建問題。在本論文中,我們利用同源模擬法(homology modeling)的概念提出了一個解決此問題的方法。首先,我們提取在PDB 中所有蛋白質結構裡的連續四個殘基片段,並由每個片段的第二、第三和第四個殘基種類對其作八千個殘基團分類。在每個殘基團中,有相似結構的片段會被群集在一起,並在其中選定一片段代表這個群集,建構片段資料庫。最後,我們在資料庫中搜尋對於目標蛋白質最有可能的片段來重建蛋白質骨架。在這裡我們使用兩個測試集驗證此方法的效能,分別為Maupetit 所提出的測試集和CASP7 對應的蛋白質子集。將實驗結果與三個先前的方法:MaxSprout、Adcock 及Maupetit 發表的SABBAC 作比較,我們的方法的重建正確性是可以與上述方法相提並論的,且在多數目標蛋白質中,我們的答案亦穩定許多。時間效率上也是令人滿意的。
Abstract
Given an amino acid sequence with the α-carbon 3D coordinates on its backbone, the all-atom protein backbone reconstruction problem (PBRP) is to rebuild the 3D coordinates of all atoms (N, C and O atoms) on the backbone. In this thesis, we propose a method for solving PBRP based on the homology modeling. First, we extract all consecutive 4-residue fragments from all protein structures in PDB. Each fragment is identified by its second, third and fourth residues. Thus, the fragments are classified into 8000 residue groups. In each residue group, the fragments with similar structures are clustered together. And one typical fragment is used to represent one cluster. These typical fragments form our fragment library. Then, we find out possible candidates in the fragment library to reconstruct the backbone of the target protein. To test the performance of our method, we use two testing sets of target proteins, one was proposed by Maupetit et al. [20] and the other is a
subset extracted from CASP7. We compare the experimental results of our method with three previous works MaxSprout, Adcock’s method, and SABBAC proposed by Maupetit et al.. The reconstruction accuracy of our method is comparable to these previous works. And the solution of our method is more stable than the previous works in most target proteins. The time efficiency of our method is also satisfactory.
目次 Table of Contents
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
Chapter 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 1
Chapter 2. Preliminaries . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.1 Properties of Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.1.1 Amino Acids in Protein . . . . . . . . . . . . . . . . . . . . . 5
2.1.2 Levels of Protein Structures . . . . . . . . . . . . . . . . 7
2.2 Protein Backbone Conformation . . . . . . . . . . . . . . . . . . . . . 12
2.3 RootMean Square Deviation . . . . . . . . . . . . . . . . . . . . . . 18
Chapter 3. Our Method . . . . . . . . . . . . . . . . . . . . . . . . . 22
3.1 Fragment Library . . . . . . . . . . . . . . . . . .. . . . . . . . . 23
3.1.1 Conformation of Fragment . . . . . . . . . . . . . . . . 23
3.1.2 Chirality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
3.1.3 Residue Group . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.1.4 Cluster . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
3.2 The Overview of OurMethod . . . . . . . . . . . . . . . . . . . . . . 27
Chapter 4. Experimental Results . . . . . . . . . . . . . . . . . . . . . . 33
Chapter 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 40
BIBLIOGRAPHY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
參考文獻 References
[1] “Centre for Molecularand and Biomolecular Informatics: Automatic Validation
of Protein Model Strucutures.” http://www.cmbi.kun.nl/mcsis/richardn/.
[2] “Critical Assessment of Techniques for Protein Structure Prediction.”
http://predictioncenter.org/, Genome Center, University of California, Davis.
[3] S. A. Adcock, “Peptide backbone reconstruction using dead-end elimination and
a knowledge-based forcefield,” Journal of Computational Chemistry, Vol. 25,
pp. 16–27, 2004.
[4] A. K. Arakaki, Y. Zhang, and J. Skolnick, “Large-scale assessment of the utility
of low-resolution protein structures for biochemical function assignment,”
Bioinformatics, Vol. 20, No. 7, pp. 1087–1096, 2004.
[5] J. L. Bell, The Art of the Intelligible: An Elementary Survey of Mathematics
in its Conceptual Development. Kluwer, 1999.
[6] H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig,
I. N. Shindyalov, and P. E. Bourne, “The Protein Data Bank,” Nucleic Acids
Research, Vol. 28, No. 1, pp. 235–242, 2000.
[7] S. Dayalan, S. Bevinakoppa, and H. Schroder, “A dihedral angle database of
short sub-sequences for protein structure prediction,” 2nd Asia-Pacific Bioinformatics
Conference (APBC), Dunedin, New Zealand, 2004.
[8] R. A. Engh and R. Huber, “Accurate bond and angle parameters for X-ray
protein structure refinement,” Acta Crystallographica, Vol. A47, pp. 392–400,
1991.
[9] H. J. Feldman and C. W. V. Hogue, “A fast method to sample real protein
conformational space,” PROTEINS: Structure, Function, and Genetics, Vol. 39,
pp. 112–131, 2000.
[10] C. Gibas and P. Jambeck, Developing Bioinformatics Computer Skills. O’Reilly
& Associates, Inc., first ed., Apr. 2001.
[11] L. Holm and C. Sander, “Database algorithm for generating protein backbone
and side-chain co-ordinates from a c alpha trace application to model building
and detection of co-ordinate errors,” Journal of Molecular Biology, Vol. 218,
pp. 183–194, 1991.
[12] J.-L. Hsin, C.-B. Yang, K.-S. Huang, and C.-N. Yang, “An ant colony optimization
approach for the protein side chain packing problem,” Proc. of the 6th
WSEAS International Conference on Microelectronics, Nanoelectronics, Optoelectronics,
Istanbul, Turkey, pp. 44–49, 2007.
[13] IUPAC-IUB Commission on Biochemical Nomenclature, “Abbreviations and
symbols for the description of the conformation of polypeptide chains,” Biochemistry,
Vol. 9, pp. 3471–3479, 1971.
[14] Y. Iwata, A. Kasuya, and S. Miyamoto, “An efficient method for reconstructing
protein backbones from α-carbon coordinates,” Journal of Molecular Graphics
and Modelling, Vol. 21, pp. 119–128, 2002.
[15] R. Kazmierkiewicz, A. Liwo, and H. A. Scheraga, “Energy-based reconstruction
of a protein backbone from its α-carbon trace by a Monte-Carlo method,”
Journal of Computational Chemistry, Vol. 23, pp. 715–723, 2002.
[16] N. Krasnogor, W. E. Hart, J. Smith, and D. A. Pelta, “Protein structure prediction
with evolutionary algorithms.,” Proceedings of the Genetic and Evolutionary
Computation Conference, Orlando, USA, 1999.
[17] T. Lezon, J. R. Banavar, and A. Maritan, “Recognition of coarse-grained protein
tertiary structure,” PROTEINS: Structure, Function and Bioinformatics,
Vol. 55, pp. 536–547, 2004.
[18] A. Liwo, M. R. Pincus, R. J. Wawak, S. Rackovsky, and H. A. Scheraga, “Calculation
of protein backbone geometry from {alpha}-carbon coordinates based
on peptide-group dipole alignment,” Protein Science, Vol. 2, pp. 1697–1714,
1993.
[19] V. N. Maiorov and G. M. Crippen, “Significance of root-mean-square deviation
in comparing three-dimensional structures of globular proteins,” Journal of
Molecular Biology, Vol. 235, pp. 625–634, 1994.
[20] J. Maupetit, R. Gautier, and P. Tuffery, “SABBAC: online structural alphabetbased
protein backbone reconstruction from alpha-carbon trace,” Nucleic Acids
Research, Vol. 34, pp. W147–W151, 2006.
[21] M. Milik, A. Kolinski, and J. Skolnick, “Algorithm for rapid reconstruction of
protein backbone from alpha carbon coordinates,” Journal of Computational
Chemistry, Vol. 18, pp. 80–85, 1997.
[22] A. G. Murzin, S. E. Brenner, T. Hubbard, and C. Chothia, “SCOP: a structural
classification of proteins database for the investigation of sequences and
structures,” Journal of Molecular Biology, Vol. 247, pp. 536–540, 1995.
[23] K. Nishikawa, F. A. Momany, and H. A. Scheraga, “Low-energy structures of
two dipeptides and their rlationship to bend conformations,” Macromolecules,
Vol. 7, No. 6, pp. 797–806, 1974.
[24] K. Nishikawa and T. Ooi, “Comparison of homologous tertiary structures of
proteins,” Journal of Theoretical Biology, Vol. 43, pp. 351–374, 1974.
[25] F. M. G. Pearl, C. F. Bennett, J. E. Bray, A. P. Harrison, N. Martin, A. Shepherd,
I. Sillitoe, J. Thornton, and C. A. Orengo, “The CATH database: an
extended protein family resource for structural and functional genomics,” Nucleic
Acids Research, Vol. 31, No. 1, pp. 452–455, 2003.
[26] G. N. Ramachandran, C. Ramakrishnan, and V. Sasisekharan, “Stereochemistry
of polypeptide chain configurations,” Journal of Molecular Biology, Vol. 7,
pp. 95–99, 1963.
[27] G. N. Ramachandran and V. Sasisekharan, “Conformation of polypeptides and
proteins,” Advances in Protein Chemistry, Vol. 23, pp. 289–437, 1968.
[28] L. S. Reid and J. M. Thornton, “Rebuilding flavodoxin from Cα coordinates:
a test study.,” Proteins, Vol. 5, pp. 170–182, 1989.
[29] J. S. Richardson, “The anatomy and taxonomy of protein structure.”
http://kinemage.biochem.duke.edu/teaching/anatax/index.html, Department
of Biochemistry, Duke University, Durham, North Carolina.
[30] I. Ruczinski, C. Kooperberg, R. Bonneau, and D. Baker, “Distributions of beta
sheets in proteins with application to structure prediction,” Proteins: Structure,
Function, and Genetics, Vol. 48, pp. 85–97, 2002.
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