Abstract
We present a formal analysis of amino acid replacement during mRNA translation. Building on an abstract stochastic model of arrival of tRNAs and their processing at the ribosome, we compute probabilities of the insertion of amino acids into the nascent polypeptide chain. To this end, we integrate the probabilistic model checker Prism in the Matlab environment. We construct the substitution matrix containing the probabilities of an amino acid replacing another. The resulting matrix depends on various parameters, including availability and concentration of tRNA species, as well as their assignment to individual codons. We draw a parallel with the standard mutation matrices like Dayhoff and PET91, and analyze the mutual replacement of biologically similar amino acids.
Partially supported by EU FP6-project ESIGNET.
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
Preview
Unable to display preview. Download preview PDF.
References
Bosnacki, D., et al.: In Silico modelling and analysis of ribosome kinetics and aa-trna competition. In: Proc. Computational Models for Cell Processes. Turku Centre for Computer Science, Åbo Academia, Turku, 16 p. (2008)
Calder, M., et al.: Analysis of signalling pathways using continuous time Markov chains. In: Priami, C., Plotkin, G. (eds.) Transactions on Computational Systems Biology VI. LNCS (LNBI), vol. 4220, pp. 44–67. Springer, Heidelberg (2006)
Chabrier, N., Fages, F.: Symbolic model checking of biochemical networks. In: Priami, C. (ed.) CMSB 2003. LNCS, vol. 2602, pp. 149–162. Springer, Heidelberg (2003)
Danos, V., et al.: Rule-based modelling of cellular signalling. In: Caires, L., Vasconcelos, V.T. (eds.) CONCUR 2007. LNCS, vol. 4703, pp. 17–41. Springer, Heidelberg (2007)
Dayhoff, M.O.: Suplements 1, 2 and 3. Atlas of Protein Sequence and Structure 5 (1978)
Dong, H., et al.: Co-variation of tRNA abundance and codon usage in Escherichia coli at different growth rates. Journal of Molecular Biology 260, 649–663 (1996)
Fluitt, A., et al.: Ribosome kinetics and aa-tRNA competition determine rate and fidelity of peptide synthesis. Computational Biology and Chemistry 31, 335–346 (2007)
Gilchrist, M.A., Wagner, A.: A model of protein translation including codon bias, nonsense errors, and ribosome recycling. Journal of Theoretical Biology 239, 417–434 (2006)
Gromadski, K.B., Rodnina, M.V.: Kinetic determinants of high-fidelity tRNA discrimination on the ribosome. Molecular Cell 13(2), 191–200 (2004)
Heath, J., et al.: Probabilistic model checking of complex biological pathways. In: Priami, C. (ed.) CMSB 2006. LNCS (LNBI), vol. 4210, pp. 32–47. Springer, Heidelberg (2006)
Heyd, A.W., Drew, D.A.: A mathematical model for elongation of a peptide chain. Bulletin of Mathematical Biology 65, 1095–1109 (2003)
Jones, D.T., et al.: The rapid generation of mutation data matrices from protein sequences. CABIOS 3, 275–282 (1992)
Karp, G.: Cell and Molecular Biology, 5th edn. Wiley, Chichester (2008)
Knudsen, C., et al.: The importance of structural transitions of the switch II region for the functions of elongation factor Tu on the ribosome. Journal of Biological Chemistry 276, 22183–22190 (2001)
Kwiatkowska, M., et al.: Probabilistic symbolic model cheking with Prism: a hybrid approach. Journal on Software Tools for Technology Transfer 6, 128–142 (2004), http://www.prismmodelchecker.org/
Pape, T., et al.: Complete kinetic mechanism of elongation factor Tu-dependent binding of aa-tRNA to the A-site of E. coli. EMBO Journal 17, 7490–7497 (1998)
Priami, C., et al.: Application of a stochastic name-passing calculus to represent action and simulation of molecular processes. Information Processing Letters 80, 25–31 (2001)
Rodnina, M.V., Wintermeyer, W.: Ribosome fidelity: tRNA discrimination, proofreading and induced fit. TRENDS in Biochemical Sciences 26(2), 124–130 (2001)
Rodnina, M.V., et al.: Codon-dependent conformational change of elongation factor Tu preceding GTP hydrolysis on the ribosome. EMBO Journal 14, 2613–2619 (1995)
Rodnina, M.V., et al.: Recognition and selection of tRNA in translation. FEBS Letters 579, 938–942 (2005)
Savelsbergh, A., et al.: An elongation factor G-induced ribosome rearrangement precedes tRNA–mRNA translocation. Molecular Cell 11, 1517–1523 (2003)
Swanson, R.: A unifying concept for the amino acid code. Bulletin of Mathematical Biology 46(2), 187–203 (1984)
Taylor, W.R.: The classification of amino acid conservation. Journal of Theoretical Biology 119, 205–218 (1986)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Bošnački, D., ten Eikelder, H.M.M., Steijaert, M.N., de Vink, E.P. (2008). Stochastic Analysis of Amino Acid Substitution in Protein Synthesis. In: Heiner, M., Uhrmacher, A.M. (eds) Computational Methods in Systems Biology. CMSB 2008. Lecture Notes in Computer Science(), vol 5307. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-88562-7_25
Download citation
DOI: https://doi.org/10.1007/978-3-540-88562-7_25
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-88561-0
Online ISBN: 978-3-540-88562-7
eBook Packages: Computer ScienceComputer Science (R0)