Abstract
Uncharged DNA analogues are frequently used to be synthesized as oligomers or combined with nucleic acids to synthesize chimeric oligomers. Owing to their special structures and the uncharged property, the oligomers with DNA analogues are useful in many applications, like fluorescence in situ hybridization (FISH), biosensors, gene chips, etc. In this study, we try to investigate the effect of an uncharged phosphate-methylated nucleotide embedded on the aptamer sequence with high affinity to IgG1 by using the computational approach. The simulation results predict that the embedded phosphate-methylated nucleotide can cause the changes in the tertiary structure and spatial charge distribution of aptamer and further influence the binding between the aptamer and IgG1. From this study, we obtain an aptamer modified with the phosphate-methylated nucleotide, named as Apt8#n10, can have an improved binding affinity to IgG1. According to these consequences, the embedded phosphate-methylated nucleotide can play a role in the aptamer sequence for tuning the binding affinity of the aptamer to its target molecule.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Wu, J., Zhu, Y., Xue, F., Mei, Z., Yao, L., Wang, X., Zheng, L., Liu, J., Liu, G., Peng, C., Chen, W.: Recent trends in SELEX technique and its application to food safety monitoring. Mikrochim. Acta 181, 479–491 (2014)
Röthlisberger, P., Hollenstein, M.: Aptamer chemistry. Adv. Drug Deliv. Rev. 134, 3–21 (2018)
Yuan, S., Zhang, N., Singh, K., Shuai, H., Chu, H., Zhou, J., Chow, B.K.C., Zheng, B.-J.: Cross-protection of influenza A virus infection by a DNA aptamer targeting the PA endonuclease domain. Antimicrob. Agents Chemother. 59, 4082–4093 (2015)
Bini, A., Mascini, M., Mascini, M., Turner, A.P.F.: Selection of thrombin-binding aptamers by using computational approach for aptasensor application. Biosens. Bioelectron. 26, 4411–4416 (2011)
Hu, W.-P., Kumar, J.V., Huang, C.-J., Chen, W.-Y.: Computational selection of RNA aptamer against angiopoietin-2 and experimental evaluation. Biomed. Res. Int. 2015, 658712 (2015)
Hsieh, P.-C., Lin, H.-T., Chen, W.-Y., Tsai, J.J.P., Hu, W.-P.: The combination of computational and biosensing technologies for selecting aptamer against prostate specific antigen. Biomed. Res. Int. 2017, 5041683 (2017)
Cai, B., Wang, S., Huang, L., Ning, Y., Zhang, Z., Zhang, G.-J.: Ultrasensitive label-free detection of PNA–DNA hybridization by reduced graphene oxide field-effect transistor biosensor. ACS Nano 8, 2632–2638 (2014)
Zheng, C., Huang, L., Zhang, H., Sun, Z., Zhang, Z., Zhang, G.-J.: Fabrication of ultrasensitive field-effect transistor DNA biosensors by a directional transfer technique based on CVD-grown graphene. ACS Appl. Mater. Interfaces 7, 16953–16959 (2015)
Zhang, G.-J., Chua, J.H., Chee, R.-E., Agarwal, A., Wong, S.M.: Label-free direct detection of MiRNAs with silicon nanowire biosensors. Biosens. Bioelectron 24, 2504–2508 (2009)
Zhang, G.-J., Zhang, G., Chua, J.H., Chee, R.-E., Wong, E.H., Agarwal, A., Buddharaju, K.D., Singh, N., Gao, Z., Balasubramanian, N.: DNA sensing by silicon nanowire: charge layer distance dependence. Nano Lett. 8, 1066–1070 (2008)
Biagetti, M., Cuccioloni, M., Bonfili, L., Cecarini, V., Sebastiani, C., Curcio, L., Giammarioli, M., DeMia, G.M., Eleuteri, A.M., Angeletti, M.: Chimeric DNA/LNA-based biosensor for the rapid detection of African swine fever virus. Talanta 184, 35–41 (2018)
Hu, W.-P., Tsai, C.-C., Yang, Y.-S., Chan, H.W.-H., Chen, W.-Y.: Synergetic improvements of sensitivity and specificity of nanowire field effect transistor gene chip by designing neutralized DNA as probe. Sci. Rep. 8, 12598 (2018)
Huang, C.-J., Lin, Z.-E., Yang, Y.-S., Chan, H.W.-H., Chen, W.-Y.: Neutralized chimeric DNA probe for detection of single nucleotide polymorphism on surface plasmon resonance biosensor. Biosens. Bioelectron. 99, 170–175 (2018)
Miyakawa, S., Nomura, Y., Sakamoto, T., Yamaguchi, Y., Kato, K., Yamazaki, S., Nakamura, Y.: Structural and molecular basis for hyperspecificity of RNA aptamer to human immunoglobulin G. RNA 14, 1154–1163 (2008)
RNAfold web server. http://rna.tbi.univie.ac.at//cgi-bin/RNAWebSuite/RNAfold.cgi. Accessed 20 Mar 2019
Hu, W.-P., Lin, H.-T., Su, W.-Y., Hu, R.-M., Yang, W., Chen, W.-Y., Tsai, J.J.P.: The molecular simulation for evaluating the binding ability of DNA aptamer to IgG. In: 7th International Conference Frontier Computing – Theory, Technologies Applications (FC 2018), p. 9 (2018)
Popenda, M., Szachniuk, M., Blazewicz, M., Wasik, S., Burke, E.K., Blazewicz, J., Adamiak, R.W.: RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures. BMC Bioinform. 11, 1–12 (2010)
Nomura, Y., Sugiyama, S., Sakamoto, T., Miyakawa, S., Adachi, H., Takano, K., Murakami, S., Inoue, T., Mori, Y., Nakamura, Y., Matsumura, H.: Conformational plasticity of RNA for target recognition as revealed by the 2.15 a crystal structure of a human IgG-aptamer complex. Nucleic Acids Res. 38, 7822–7829 (2010)
Kolovskaya, O.S., Zamay, T.N., Zamay, A.S., Glazyrin, Y.E., Spivak, E.A., Zubkova, O.A., Kadkina, A.V., Erkaev, E.N., Zamay, G.S., Savitskaya, A.G., Trufanova, L.V., Petrova, L.L., Berezovski, M.V.: DNA-aptamer/protein interaction as a cause of apoptosis and arrest of proliferation in Ehrlich ascites adenocarcinoma cells. Biochem. Suppl. Ser. A Membr. Cell Biol. 8, 60–72 (2014)
Cai, S., Yan, J., Xiong, H., Liu, Y., Peng, D., Liu, Z.: Investigations on the interface of nucleic acid aptamers and binding targets. Analyst 143, 5317–5338 (2018)
Hu, W.-P., Lin, H.-T., Tsai, J.J.P., Chen, W.-Y.: Investigating interactions between proteins and nucleic acids by computational approaches. In: Computational Methods with Applications Bioinformatics Analysis, 1st ed., pp. 98–117. World Scientific, Singapore (2017)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Singapore Pte Ltd.
About this paper
Cite this paper
Hu, WP., Lin, HT., Chen, WY., Tsai, J.J.P. (2020). A Study on the Effect of an Aptamer with an Embedded Phosphate-Methylated Nucleotide on the Binding of a Target Molecule Using Molecular Simulation. In: Hung, J., Yen, N., Chang, JW. (eds) Frontier Computing. FC 2019. Lecture Notes in Electrical Engineering, vol 551. Springer, Singapore. https://doi.org/10.1007/978-981-15-3250-4_4
Download citation
DOI: https://doi.org/10.1007/978-981-15-3250-4_4
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-3249-8
Online ISBN: 978-981-15-3250-4
eBook Packages: Intelligent Technologies and RoboticsIntelligent Technologies and Robotics (R0)