臺灣博碩士論文加值系統

Single-stranded DNA or RNA molecules (Aptamers) which bind to selected target proteins are in the attention for computational docking studies. With advent of different simulation procedures, the selection of nucleic acid aptamers that binds to proteins tightly and specifically has become efficient. Discovery Studio 3.5 is a modeling and simulation software package for both small and macromolecule study. Firstly a comparative study was carried out to analyze the consistency of the docking score between thrombin and its aptamers from literature studies. A rigid-body docking procedure, ZDOCK which uses Pairwise Shape Complementarity (PSC) function has provided reliable results for thrombin and its aptamers and was consistent with previous study.
Angiopoietin-2 (Ang2) displays its appearance in the change vasculature of human tumors. With aim to introduce computational simulation approach to screen high binding aptamers for angiopoietin-2 (Ang2), we used ZRANK from Discovery studio 3.5 and studied the interactions between Ang2 and its aptamers from literature. Based on ZRANK scores obtained, three high binding affinity aptamers were selected. 189 sequences with two-point mutations were produced from three scrutinized high binding aptamers and simulated with Ang2.
Although ZDOCK and ZRANK set as alternative method to in silico selection of aptamers, the resulted simulation aptamers may prove difficult to adapt for biosensor applications. We therefore attempted to develop selection method for aptamers. Surface plasmon resonance (SPR) biosensor was used to test the binding affinity of high and low ZRANK score Ang2/aptamers. A particular RNA aptamer showed higher binding affinity and SPR response to Ang2 than reported in literature. Using ZRANK scoring function, this is the first study of the in silico selection of aptamers against Ang2.

Single-stranded DNA or RNA molecules (Aptamers) which bind to selected target proteins are in the attention for computational docking studies. With advent of different simulation procedures, the selection of nucleic acid aptamers that binds to proteins tightly and specifically has become efficient. Discovery Studio 3.5 is a modeling and simulation software package for both small and macromolecule study. Firstly a comparative study was carried out to analyze the consistency of the docking score between thrombin and its aptamers from literature studies. A rigid-body docking procedure, ZDOCK which uses Pairwise Shape Complementarity (PSC) function has provided reliable results for thrombin and its aptamers and was consistent with previous study.
Angiopoietin-2 (Ang2) displays its appearance in the change vasculature of human tumors. With aim to introduce computational simulation approach to screen high binding aptamers for angiopoietin-2 (Ang2), we used ZRANK from Discovery studio 3.5 and studied the interactions between Ang2 and its aptamers from literature. Based on ZRANK scores obtained, three high binding affinity aptamers were selected. 189 sequences with two-point mutations were produced from three scrutinized high binding aptamers and simulated with Ang2.
Although ZDOCK and ZRANK set as alternative method to in silico selection of aptamers, the resulted simulation aptamers may prove difficult to adapt for biosensor applications. We therefore attempted to develop selection method for aptamers. Surface plasmon resonance (SPR) biosensor was used to test the binding affinity of high and low ZRANK score Ang2/aptamers. A particular RNA aptamer showed higher binding affinity and SPR response to Ang2 than reported in literature. Using ZRANK scoring function, this is the first study of the in silico selection of aptamers against Ang2.

Contents
Abstract 3
Acknowledgements 4

Chapter 1 Introduction 9
1.1 Background 10
1.2 Topics of Study 11
1.2.1 The interaction of Thrombin and Aptamer 11
1.2.2 The interaction of Aptamers and Angiopoietin-2 12
1.3 Motivations and objectives 13
1.4 Research Framework of the dissertation 14

Chapter 2 Literature Review
2.1 Molecular simulations on interactions between protein and nucleic acids 16
2.2 DNA/Protein and RNA/Protein interactions 16
2.3 Basic theory of SPR Biosensors 17

Chapter 3 Materials and Methods
3.1 Collecting Protein Structures 20
3.2 Construction of DNA aptamers for Thrombin 22
3.3 Construction of RNA aptamers for Angiopoietin-2 23
3.4 Simulation methods: ZDOCK and ZRANK 27
3.4.1 ZDOCK Simulation between Thrombin/Aptamers 28
3.4.2 ZRANK Simulation between Ang2/Aptamers 28
3.4.3 Generation of Mutant Aptamers to Ang2 29
3.5 SPRi Experimental Procedure 31
3.5.1 Experimental reagents and SPRi Technique 31

Chapter 4 Results and discussion
4.1 Simulations of thrombin/aptamer interactions by using ZDOCK 34
4.2 Selecting Ang2-specific aptamers by using ZRANK method 36
4.3 Experimental evaluations for the selected Ang2 aptamers 46

Chapter 5 Conclusion
5.1 Summary 49
5.2 Recommendations and Perspectives 50
Appendix A 51
Appendix B 52
References 53

List of Tables
Table 1 Thrombin binding aptamer sequences 22
Table 2 Ang2-specific aptamers collected from literature 23
Table 3 Dot-bracket notation information of Ang2 aptamer sequences 24
Table 4 Nucleotides involved in binding interaction to Ang2 30
Table 5 Selected RNA aptamers used for SPR experiment 32
Table 6 Comparing ZDOCK results of thrombin/aptamer to literature 35
Table 7 ZRANK scores of each Ang2/aptamers complex 37
Table 8 189 mutated RNA aptamer sequences generated from three
high binding aptamers (Seq1, Seq2, Seq15) 38
Table 9 Experimental data and the computationally obtained scores 47


List of Figures
Figure 1 Research framework chart for aptamer selection process 15
Figure 2 Principle of Surface plasmon resonance in Biacore system 18
Figure 3 Isolated structure of Thrombin from 1HAO complex 20
Figure 4 Structure of Ang2 from 2GY7 complex 21
Figure 5 3D structures of Thrombin binding aptamers 22
Figure 6 3D structures of Ang2-specific aptamers 25
Figure 7 A schematic representations of the mixed BAT/PEG
thiol layer, streptavidin, and biotinylated RNA aptamers on the SPR sensor surface 32
Figure 8 Top binding pose of Thrombin/aptamers ZDOCK results 34
Figure 9 ZRANK results of Ang2/aptamer complexes 36
Figure 10 ZRANK results Ang2/mutated-aptamer complexes 44
Figure 11 SPR sensorgrams for interactions between immobilized
Ang2 and different aptamers. 46

[1]O. D. Wei Wang, Carolina M Reyes, Peter A Kollman, "Biomolecular simulations- Recent developments in force fields, simulations of enzyme catalysis, protein-ligand, protein-protein, and protein-nucleic acid noncovalent interactions," Annual Review of Biophysics and Biomolecular Structure, vol. 30, pp. 211-243, 2001.
[2]D. Chandler, "Interfaces and the driving force of hydrophobic assembly," Nature, vol. 473, pp. 640-647, 2005.
[3]S. A. B. Ailan Cheng, Kenneth M Merz Jr, Charles H Reynolds, "GB-SA water model for the Merck molecular force field (MMFF)," Journal of Molecular Graphics and Modelling, vol. 18, pp. 273-282, 2000.
[4]J. Alexander D Mackerell, "Empirical force fields for biological macromolecules: overview and issues," Journal of Computational Chemistry, vol. 25, pp. 1584-1604, 2004.
[5]C. L. B. I. B R Brooks, A D Mackerell Jr., L Nilsson, R J Petrella, B Roux, Y Won, G Archontis, C Bartels, S Boresch, A Caflisch, L Caves, Q Cui, A R Dinner, M Feig, S Fischer, J Gao, M Hodoscek, W IM, K Kuczera, T Lazaridis, J MA, V ovchinnikov, E Paci, R W Pastor, C B Post, J Z PU, M Schaefer, B Tidor, R M Venable, H L Woodcock, X WU, W Yang, D M York, M Karplus, "CHARMM: the biomolecular simulation program," Journal of Computational Chemistry, vol. 30, pp. 1545-1614, 2009.
[6]J. M. Rong Chen, Joel Janin, Zhiping Weng, "A protein-protein docking benchmark," PROTEINS: Structure, Function, and Genetics, vol. 52, pp. 88-91, 2003.
[7]B. P. a. Z. Weng, "A combination of rescoring and refinement significantly improves protein docking performance," Proteins, vol. 72, pp. 270-279, 2008.
[8]J. Z. Ka-To Shum, John J. Rossi, "Nucleic Acid Aptamers as Potential Therapeutic and Diagnostic Agents for Lymphoma," Journal of Cancer Therapy, vol. 4, pp. 872-890, 2013.
[9]A. D. E. J. W. Szostak, "In Vitro Selection of RNA Molecules that Bind Specific Ligands," Nature, vol. 346, pp. 818-822, 1990.
[10]J. C. Xu Wu, Min Wu, Julia Xiaojun Zhao, "Aptamers: active targeting ligands for cancer diagnosis and therapy," Theranostics, vol. 5, pp. 322-344, 2015.
[11]S. L. a. C. B. Kyung-Mi Song, "Aptamers and their biological applications," Sensors (Basel), vol. 12, pp. 612-631, 2012.
[12]S. D. Jayasena, "Aptamers- An Emerging Class of Molecules That Rival Antibodies in Diagnostics," Clinical Chemistry, vol. 45, pp. 1628–1650, 1999.
[13]D. J. P. Thomas hermann, "Adaptive recognition by nucleic acid aptamers," Science, vol. 287, pp. 820-825, 2000.
[14]B. C. S. K. Oliphant AR, "Defining the Sequence Specificity of DNA-Binding Proteins by Selecting Binding Sites from Random-Sequence Oligonucleotides: Analysis of Yeast GCN4 Protein," Molecular and Cellular Biology, vol. 9, pp. 2944-2949, 1989.
[15]M. M. S. Tombelli, M. Mascini, "Analytical applications of aptamers," Biosensors and Bioelectronics, vol. 20, pp. 2424-34, 2005.
[16]J. P. K. Yun Hwa Kim, Se Jong Han, Sang Jun Sim, "Aptamer biosensor for lable-free detection of human immunoglobulin E based on surface plasmon resonance," Sensors and Actuators B: Chemical, vol. 139, pp. 471-475, 2009.
[17]M. M. Sara Tombelli, Marco Mascini, "Aptamers-based assays for diagnostics, environmental and food analysis," Biomolecular Engineering, vol. 24, pp. 191-200, 2007.
[18]R. L. Jinli Wang, Jingjuan Xu, Danke Xu, Hongyuan Chen, "Characterizing the interaction between aptamers and human IgE by use of surface plasmon resonance," Analytical and Bioanalytical Chemistry, vol. 390, pp. 1059-1065, 2008.
[19]A. P. Yun Lin, KATHLEEN M MORDEN, SUMEDHA D JAYASENA, "Peptide conjugation to an in vitro-selected DNA ligand improves enzyme inhibition," Proceedings of the National Academy of Sciences of the United States of America, vol. 92, pp. 11044-11048, 1995.
[20]A. W. S. Mark F Kubik, Dan Schneider, Richard A Marlar, Diane Tasset, "High-affinity RNA ligands to human α-thrombin," Nucleic Acids Research, vol. 22, pp. 2619-2626, 1994.
[21]M. F. K. Diane M Tasset, Walter Steiner, "Oligonucleotide inhibitors of human thrombin that bind distinct epitopes," Journal of Molecular Biology, vol. 272, pp. 688-698, 1997.
[22]S. V. Qing Zhang, Philip E Bourne, "Overview of Structural Bioinformatics," Bioinformatics Technologies, pp. 15-44, 2005.
[23]J. P. P. Markus G Grutter, Joseph Rahuel, Hugo Grossenbacher, Wolfram Bode, Jan Hofsteenge, Stuart R Stone, "Crystal structure of the thrombin-hirudin complex- a novel mode of serine protease inhibition," The EMBO Journal, vol. 9, pp. 2361 -2365, 1990.
[24]M. J. F. John W Fenton, Anne B Stackrow, "Human thrombins. Production, evaluation, and properties of alpha-thrombin," The Journal of Biological Chemistry, vol. 252, pp. 3587-3598, 1977.
[25]I. M. W Bode, U Baumann, R Huber, S R Stone, J Hofsteenge, "The refined 1.9 A crystal structure of human alpha-thrombin- interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment," The EMBO Journal, vol. 8, pp. 3467 - 3475, 1989.
[26]K. G. R. Timothy J Rydel, A tulinsky, Wolfarm Bode, Robert Huber, Carolyn Roitsh, John W Fenton II, "The Structure of a Complex of Recombinant Hirudin and Human (alpha)-Thrombin," Science, vol. 249, pp. 277-280, 1990.
[27]K. P. P. Kaillathe Padmanabhang, Joseph D Ferrarag, J Evan Sadled, Alexander Tulinsky, "The structure of alpha-thrombin inhibited by a 15-mer single-stranded DNA aptamer," The Journal of Biological Chemisrty, vol. 268, pp. 17651-17654, 1993.
[28]J. F. Jennifer A Kelly, Todd O Yeates, "Reconciliation of the X-ray and NMR Structures of the Thrombin-Binding Aptamer d(GGTTGGTGTGGTTGG)," Journal of Molecular Biology, vol. 256, pp. 417-422, 1996.
[29]P. S. Roman F Macaya, Flint W Smith, James A Roe, Juli Feigon, "Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution," Proceedings of the National Academy of Sciences of the United States of America, vol. 90, pp. 3745-3749, 1993.
[30]M. M. Alessandra Bini, Marco Mascini, Anthony P.F. Turner, "Selection of thrombin-binding aptamers by using computational approach for aptasensor application," Biosensors and Bioelectronics, vol. 26, pp. 4411-4416, 2011.
[31]R. L. Moritz Felcht, Alexander Schering, Philipp Seidel, Kshitij Srivastava, Junhao Hu, Arne Bartol, Yvonne Kienast, Christiane Vettel, Elias K. Loos, Simone Kutschera, Susanne Bartels, Sila Appak, Eva Besemfelder, Dorothee Terhardt, Emmanouil Chavakis, Thomas Wieland, Christian Klein, Markus Thomas, Akiyoshi Uemura, Sergij Goerdt, and Hellmut G. Augustin, "Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling," The Journal of Clinical Investigation, vol. 122, pp. 1991-2005, 2012.
[32]S. D. George D. Yancopoulos, Nicholas W. Gale, John S. Rudge, Stanley J. Wiegand & Jocelyn Holash, "Vascular-specific growth factors and blood vessel formation," Nature, vol. 407, pp. 242-248, 2000.
[33]S. A. M. Brunna E Alves, Franciso JP Aranha, Tania FG Siegl, Carmino A Souza, Irene Lorand-Metze, and J. M. A.-B. a. E. V. D. Paula, "Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia," BMC Infectious Diseases, vol. 10, p. 143, 2010.
[34]C. S. Peter C Maisonpierre, Pamela F Jones, Sona Bartunkova, Stanley J Wiegand, Czeslaw Radziejewski, Debra Compton, Joyce McClain, Thomas H Aldrich, Nick Papadopoulos, Thomas J Daly, Samuel Davis, Thomas N Sato, George D Yancopoulos, "Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis," Science, vol. 277, pp. 55-60, 1997.
[35]H. I. Tsuyoshi Etoh, Shinji Tanaka, Graham F. Barnard, Seigo Kitano, and Masaki Mori, "Angiopoietin-2 Is Related to Tumor Angiogenesis in Gastric Carcinoma: Possible in Vivo Regulation via Induction of Proteases," Cancer Research, vol. 61, pp. 2145-2153, 2001.
[36]M. M. Shinji Tanaka, Yoshihiro Sakamoto, Masatoshi Makuuchi, Keizo Sugimachi, and Jack R. Wands, "Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma," The Journal of Clinical Investigation, vol. 103, pp. 341–345, 1999.
[37]W. R. Astrid Stratmann, and Karl H. Plate, "Cell Type-Specific Expression of Angiopoietin-1 and Angiopoietin-2 Suggests a Role in Glioblastoma Angiogenesis," American Journal of Pathology, vol. 153, pp. 1459-1466, 1998.
[38]W. L. Syed A. Ahmad, Young D. Jung, Fan Fan, Niels Reinmuth, Corazon D. Bucana, Lee M. Ellis, "Differential Expression of Angiopoietin-1 and Angiopoietin-2 in Colon Carcinoma," Cancer, vol. 92, pp. 1138-1143, 2001.
[39]A. H. David Z, David R. Friedlander, Wai Chan, Jocelyn Holash, Stanley J. Wiegand, George D. Yancopoulos, and Martin Grumet, "In Situ Expression of Angiopoietins in Astrocytomas Identifies Angiopoietin-2 as an Early Marker of Tumor Angiogenesis," Experimental Neurology, vol. 159, pp. 391-400, 1999.
[40]C. J. Brown, S. G. Dastidar, H. Y. See, D. W. Coomber, M. Ortiz-Lombardia, C. Verma, et al., "Rational design and biophysical characterization of thioredoxin-based aptamers: insights into peptide grafting," J Mol Biol, vol. 395, pp. 871-83, Jan 29 2010.
[41]M. T. Patrick Nasarre, Karoline Kruse, Iris Helfrich, Vivien Wolter, Carleen Deppermann, Dirk Schadendorf, Gavin Thurston, Ulrike Fiedler and Hellmut G Augustin, "Host-derived angiopoietin-2 affects early stages of tumor development and vessel maturation but is dispensable for later stages of tumor growth," Cancer Research, vol. 69, pp. 1324-1333, 2009.
[42]B. L. F. Hiroya Hashizume, Takashi Kuroda, Peter Baluk, Angela Coxon, Dongyin Yu, and J. D. O. James V. Bready, and Donald M. McDonald, "Complementary actions of inhibitors of angiopoietin-2 and VEGF on tumor angiogenesis and growth," Cancer Research, vol. 70, pp. 2213-23, 2010.
[43]A. B. Hanhua Huang, Gary Woodnutt and Rodney Lappe, "Targeting the ANGPT-TIE2 pathway in malignancy," Nature Reviews Cancer, vol. 10, pp. 575-85, 2010.
[44]F. P. Roberta Mazzieri, Davide Moi, Erika Zonari, Anna Ranghetti, Alvise Berti, Letterio S. Politi, Bernhard Gentner, Jeffrey L. Brown, Luigi Naldini, and Michele De Palma, "Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells," Cancer Cell, vol. 19, pp. 512-26, 2011.
[45]H.-Z. K. Young Jun Koh, Seong-Ik Hwang, Jeung Eun Lee, Nuri Oh, Keehoon Jung, Minah Kim, Kyung Eun Kim, Homin Kim, Nam-Kyu Lim, Choon-Ju Jeon, Gyun Min Lee, Byeong Hwa Jeon, Do-Hyun Nam, and A. N. Hoon Ki Sung, Ook Joon Yoo, Gou Young Koh, "Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage," Cancer Cell, vol. 18, pp. 171-84, 2010.
[46]S. S. White Rebekah R, Rusconi Christopher P, Shetty Geetha, Dewhirst Mark W, Kontos Christopher D, Sullenger Bruce A, "Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2," Proceedings of the National Academy of Sciences of the United States of America, vol. 100, pp. 5028-5033, 2003.
[47]M. D. Shiva Sarraf-Yazdi, Jing Mi, M.D., Ph.D., Benjamin J. Moeller, M.D., Xilin Niu, M.D., Rebekah R. White, M.D., Christopher D. Kontos, M.D., Bruce A. Sullenger, Ph.D., Mark W. Dewhirst, D.V.M., Ph.D., and Bryan M. Clary, M.D., "Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer," Journal of Surgical Research, vol. 146, pp. 16-23, 2008.
[48]M. O. S. Yaroslav Chushak, "In silico selection of RNA aptamers," Nucleic Acids Research, vol. 37, p. e87, 2009.
[49]d. S. Ioannis Xenarios, Xiaoqun Joyce Duan, Patrick Higney, Sul-Min Kim, David Eisenberg, "DIP, the Database of Interacting Proteins- a research tool for studying cellular networks of protein interactions," Nucleic Acids Research, vol. 30, pp. 303-305, 2002.
[50]D. R. Paul Shannon, Andrew Markiel, Nada Amin, Owen Ozier, Nitin S Baliga, Benno Schwikowski, Trey Ideker, "Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks," Genome Research, vol. 12, pp. 47-56, 2002.
[51]M. S. Yong Xiong, "Protein–Nucleic Acid Interaction: Major Groove Recognition Determinants. eLS. ." 2001.
[52]R. A. L. Nicholas M Luscombe, Janet M Thornton, "Amino acid–base interactions: a three-dimensional analysis of protein–DNA interactions at an atomic level," Nucleic Acids Research, vol. 29, pp. 2860-2874, 2001.
[53]H. M. Yael Mandel-Gutfreund, "Quantitative parameters for amino acid–base interaction: implications for prediction of protein–DNA binding sites," Nucleic Acids Research, vol. 26, pp. 2306–2312, 1998.
[54]J. M. R. Nadrian C Seeman, Alexander Rich, "Sequence-specific recognition of double helical nucleic acids by proteins," Proceedings of the National Academy of Sciences of the United States of America, vol. 73, pp. 804-808, 1976.
[55]O. G. a. A. D. M. Jr, "Computational evaluation of protein-small molecule binding," Current Opinion in Structural Biology, vol. 19, pp. 56-61, 2009.
[56]S. G. D. Christopher J. Brown, Hai Yun See, David W. Coomber, Miguel Ortiz-Lombardía, Chandra Verma and David P. Lane, "Rational design and biophysical characterization of thioredoxin-based aptamers: insights into peptide grafting," Journal of Molecular Biology, vol. 395, pp. 871-883, 2010.
[57]P. I. A. Karen Muthusamy, Patrick Govender, Hendrik G. Kruger, Glenn E. M. Maguire, Thavendran Govender, "Design and study of peptide-based inhibitors of amylin cytotoxicity," Bioorganic & Medicinal Chemistry Letters, vol. 20, pp. 1360-1362, 2010.
[58]L.-L. L. Qi Huang, Sheng-Yong Yang, "PhDD: A new pharmacophore-based de novo design method of drug-like molecules combined with assessment of synthetic accessibility," Journal of Molecular Graphics and Modelling, vol. 28, pp. 775-787, 2010.
[59]R. M. J. a. M. J. E. S. Henry A. Gabb, "Modeling protein docking using shape complementarity, electrostatics and biochemical information," 1997.
[60]V. A. R. Jeffrey G Mandell, Michael E Pique, Vladimir Kotlovyi, Julie C Mitchell, Erik Nelson, Igor Tsigelny, Lynn F Ten Eyck, "Protein docking using continuum electrostatics and geometric fit," Protein Engineering, vol. 14, pp. 105-113, 2001.
[61]I. A. Vakser, "Evaluation of GRAMM low-resolution docking methodology on the hemagglutinin-antibody complex," Proteins, vol. 1, pp. 226-230, 1997.
[62]D. H. J. B. a. P. G. Stockley, "Aptamers come of age - at last," Nature Reviews Microbiology, vol. 4, pp. 588-96, 2006.
[63]P. A. De Luca Laura, Vistoli Giulio, Letizia Barreca Maria, Villa Luigi, Monforte Pietro, Chimirri Alba, "Analysis of the full-length integrase–DNA complex by a modified approach for DNA docking," Biochemical and Biophysical Research Communications, vol. 310, pp. 1083-1088, 2003.
[64]H. A. G. Michael J E Sternberg, Richard M Jackson, "Predictive docking of protein—protein and protein—DNA complexes," Current Opinion in Structural Biology, vol. 8, pp. 250-256, 1998.
[65]A. D. J. v. D. Marc van Dijk, Victor Hsu, Rolf Boelens and Alexandre M. J. J. Bonvin, "Information-driven protein-DNA docking using HADDOCK: it is a matter of flexibility," Nucleic Acids Research, vol. 34, pp. 3317-3325, 2006.
[66]D. T. A. D. Susan Jones, Nicholas M Luscombe, Helen M Berman, Janet M Thornton, "Protein–RNA interactions- a structural analysis," Nucleic Acids Research, vol. 29, pp. 943-954, 2001.
[67]W. D. Wilson, "Analyzing biomolecular interactions," Science, vol. 295, pp. 2103-2105, 2002.
[68]A. V. H. Patrick Englebienne, Michel Verhas, "Surface plasmon resonance- principles, methods and applications in biomedical sciences.," Journal of Spectroscopy, vol. 17, pp. 255-273, 2003.
[69]S. F. Eric M Phizicky, "Protein–protein interactions- methods for detection and analysis," Microbiological reviews, vol. 59, pp. 94-123, 1995.
[70]M. M. Simona Scarano, Anthony P.F. Turner, Maria Minunni, "Surface plasmon resonance imaging for affinity-based biosensors," Biosensors and Bioelectronics, vol. 25, pp. 957-966, 2010.
[71]C. Guiducci, "Surface plasmon resonance systems," Surface Plasmon Resonance Handout, pp. 1-28, 2011.
[72]H. L. Emeline Bouffartigues, Marielle Anger-Leroy, Sylvie Rimsky and Malcolm Buckle, "Rapid coupling of Surface Plasmon Resonance (SPR and SPRi) and ProteinChip based mass spectrometry for the identification of proteins in nucleoprotein interactions," Nucleic Acids Research, vol. 35, p. e39, 2007.
[73]L. H. Nogues C, Langendorf C G, Law R H, Buckle A M, Buckle M, "Characterisation of peptide microarrays for studying antibody-antigen binding using surface plasmon resonance imagery," PLoS One, vol. 5, p. e12152, 2010.
[74]H. H. P. Wong C L, Suen Y K, Kong S K, Chen Q L, Yuan W, Wu S Y, "Real-time protein biosensor arrays based on surface plasmon resonance differential phase imaging," Biosensors and Bioelectronics, vol. 24, pp. 606-612, 2008.
[75]T. E. G. Bryce P Nelson, Mark R Liles, Robert M Goodman, and Robert M Corn, "Surface Plasmon Resonance Imaging Measurements of DNA and RNA Hybridization Adsorption onto DNA Microarrays," Analytical Chemistry, vol. 73, pp. 1-7, 2001.
[76]L. X. Andrei Kouranov, Joanna de la Cruz, Li Chen, John Westbrook, Philip E. Bourne and Helen M. Berman, "The RCSB PDB information portal for structural genomics," Nucleic Acids Research, vol. 34, pp. D302–D305, 2006.
[77]T. A. Padmanabhan K, "An ambiguous structure of a DNA 15-mer thrombin complex," Acta Crystallographica Section D Biological Crystallography, vol. 52, pp. 272-282, 1996.
[78]D. T.-R. William A Barton, Edward P Miranda, Momchil V Kolev, Kanagalaghatta R Rajashankar, Juha P Himanen & Dimitar B Nikolov, "Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex," Nature Structural & Molecular Biology, vol. 13, 2006.
[79]R. J. A. White R R., Viles K D, Sullenger B A., Kontos C D, "A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function," Angiogenesis, vol. 11, pp. 395-401, 2008.
[80]M. H. Kengo Sato, Kiyoshi Asai and Toutai Mituyama, "CENTROIDFOLD: a web server for RNA secondary structure prediction," Nucleic Acids Research, vol. 37, pp. W277–W280, 2009.
[81]M. S. Mariusz Popenda, Maciej Antczak, Katarzyna J. Purzycka, Piotr Lukasiak, Natalia Bartol, Jacek Blazewicz and Ryszard W. Adamiak, "Automated 3D structure composition for large RNAs," Nucleic Acids Research, vol. 40, p. e112, 2012.
[82]R. C. a. Z. Weng, "A Novel Shape Complementarity Scoring Function for Protein-Protein Docking," PROTEINS: Structure, Function, and Genetics, vol. 51, pp. 397–408, 2003.
[83]R. M. J. Henry A Gabb, Michael J E Sternberg, "Modelling protein docking using shape complementarity, electrostatics and biochemical information," Journal of Molecular Biology, vol. 272, pp. 106-120, 1997.
[84]R. C. a. Z. Weng, "Docking unbound proteins using shape complementarity, desolvation, and electrostatics," PROTEINS: Structure, Function, and Genetics, vol. 47, pp. 281-294, 2002.
[85]S. V. a. C. J. Camacho, "Protein–protein docking: is the glass half-full or half-empty?," TRENDS in Biotechnology, vol. 22, pp. 110-116, 2004.
[86]G. V. Chao Zhang, James L Cornette, Charles DeLisi, "Determination of atomic desolvation energies from the structures of crystallized proteins," Journal of Molecular Biology, vol. 267, pp. 707-726, 1997.
[87]S. Q. a. H.-X. Zhou, "Structural Models of Protein-DNA Complexes Based on Interface Prediction and Docking," Current Protein & Peptide Science, vol. 12, pp. 531–539, 2011.
[88]S. Q. a. H.-X. Z. Harianto Tjong, "PI2PE: protein interface/interior prediction engine," Nucleic Acids Research, vol. 35, pp. W357–W362, 2007.
[89]W. Z. Pierce B, "ZRANK: reranking protein docking predictions with an optimized energy function," PROTEINS: Structure, Function, and Bioinformatics, vol. 67, pp. 1078–1086, Jun 1 2007.
[90]L. M. B. Long S B, White R R, Sullenger B A, "Crystal structure of an RNA aptamer bound to thrombin," RNA, vol. 14, pp. 2504-2512, 2008.
[91]C. G. L. Wen-Pin Hu, Chen S J, Kuo Y M, "Kinetic analysis of beta-amyloid peptide aggregation induced by metal ions based on surface plasmon resonance biosensing," Journal of Neuroscience Methods, vol. 154, pp. 190-197, 2006.
[92]T. D. Barton W A, Nikolov D B, "Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition," Structure, vol. 13, pp. 825-832, 2005.
[93]G. Schreiber, "Kinetic studies of protein-protein interactions," Current Opinion in Structural Biology, vol. 12, pp. 41-47, 2002.
[94]K. A. Nasa Savory, Koji Sode, Kazunori Ikebukuro, "Selection of DNA aptamer against prostate specific antigen using a genetic algorithm and application to sensing," Biosensors and Bioelectronics, vol. 26, pp. 1386-1391, 2010.