Research article Special Issues

Dynamics analysis of building block synthesis reactions for virus assembly in vitro

  • Received: 28 October 2022 Revised: 02 December 2022 Accepted: 12 December 2022 Published: 19 December 2022
  • Virus assembly from structural protein monomers to virus shells is a key step of virus replication. Some drug targets were found in this process. It consists of two steps. Virus structural protein monomers firstly polymerize to building blocks, then these building blocks assemble into virus shells. So, these building block synthesis reactions in the first step are fundamental for virus assembly. Typically, virus building blocks are made up of less than six monomers. They are of five types, including dimer, trimer, tetramer, pentamer and hexamer. In this work, we develop five synthesis reaction dynamical models for these five types, respectively. Then, we prove the existence and uniqueness of the positive equilibrium solution for these dynamical models one by one. Subsequently, we also analyze the stability of the equilibrium states, respectively. We got the function of monomer and dimer concentrations for dimer building blocks in the equilibrium state. We also got the function of all intermediate polymers and monomers for trimer, tetramer, pentamer and hexamer building blocks in the equilibrium state, respectively. Based on our analysis, dimer building blocks in the equilibrium state will decrease as the ratio of the off-rate constant to the on-rate constant increases. Trimer building blocks in the equilibrium state will decrease with the increasing ratio of the off-rate constant to the on-rate constant of trimers. These results may provide further insight into the virus-building block synthesis dynamic property in vitro.

    Citation: Yuewu Liu, Mengfang Zeng, Shengyong Liu, Chun Li. Dynamics analysis of building block synthesis reactions for virus assembly in vitro[J]. Mathematical Biosciences and Engineering, 2023, 20(2): 4082-4102. doi: 10.3934/mbe.2023191

    Related Papers:

  • Virus assembly from structural protein monomers to virus shells is a key step of virus replication. Some drug targets were found in this process. It consists of two steps. Virus structural protein monomers firstly polymerize to building blocks, then these building blocks assemble into virus shells. So, these building block synthesis reactions in the first step are fundamental for virus assembly. Typically, virus building blocks are made up of less than six monomers. They are of five types, including dimer, trimer, tetramer, pentamer and hexamer. In this work, we develop five synthesis reaction dynamical models for these five types, respectively. Then, we prove the existence and uniqueness of the positive equilibrium solution for these dynamical models one by one. Subsequently, we also analyze the stability of the equilibrium states, respectively. We got the function of monomer and dimer concentrations for dimer building blocks in the equilibrium state. We also got the function of all intermediate polymers and monomers for trimer, tetramer, pentamer and hexamer building blocks in the equilibrium state, respectively. Based on our analysis, dimer building blocks in the equilibrium state will decrease as the ratio of the off-rate constant to the on-rate constant increases. Trimer building blocks in the equilibrium state will decrease with the increasing ratio of the off-rate constant to the on-rate constant of trimers. These results may provide further insight into the virus-building block synthesis dynamic property in vitro.



    加载中


    [1] M. J. Roossinck, Virus, Princeton University Press, Princeton, 2016.
    [2] W. S. Ryu, Molecular Virology of Human Pathogenic Viruses, Academic Press, 2017.
    [3] B. Hu, H. Guo, P. Zhou, Characteristics of SARS-CoV-2 and COVID-19, Nat. Rev. Microbiol., 19 (2021), 141–154. https://doi.org/10.1038/s41579-020-00459-7 doi: 10.1038/s41579-020-00459-7
    [4] K. Mayo, J. Mcdermott, E. Barklis, Hexagonal organization of moloney murine leukemia virus capsid proteins, Virology, 298 (2002), 30–38. https://doi.org/10.1006/viro.2002.1452 doi: 10.1006/viro.2002.1452
    [5] X. Xiong, K. Qu, K. A. Ciazynska, M. Hosmillo, J. Briggs, A thermostable, closed, SARS-CoV-2 spike protein trimer, Nat. Struct. Mol. Biol., 27 (2020), 934–941. https://doi.org/10.1038/s41594-020-0478-5 doi: 10.1038/s41594-020-0478-5
    [6] A. Christiansen, M. Weiel, A. Winkler, A. Schug, J. Reinstein, The trimeric major capsid protein of mavirus is stabilized by its interlocked N-termini enabling core flexibility for capsid assembly, J. Mol. Biol., 433 (2021), 166859. https://doi.org/10.1016/j.jmb.2021.166859 doi: 10.1016/j.jmb.2021.166859
    [7] E. Dan, A. Zlotnick, Model-based analysis of assembly kinetics for virus capsids or other spherical polymers, Biophys. J., 83 (2002), 1217–1230. https://doi.org/10.1016/S0006-3495(02)75245-4 doi: 10.1016/S0006-3495(02)75245-4
    [8] Y. W. Liu, X. F. Zou, Mathematical modeling of HIV-like particle assembly in vitro, Math. Biosci., 288 (2017), 46–51. https://doi.org/10.1016/j.mbs.2017.02.010 doi: 10.1016/j.mbs.2017.02.010
    [9] Y. W. Liu, X. F. Zou, A new model system for exploring assembly mechanisms of the HIV-1 immature capsid in vivo, B. Math. Biol., 81 (2019), 1506–1526. https://doi.org/10.1007/s11538-019-00571-7 doi: 10.1007/s11538-019-00571-7
    [10] J. K. Hyun, M. Radjainia, R. L. Kingston, A. K. Mitra, Proton-driven assembly of the rous sarcoma virus capsid protein results in the formation of icosahedral particles, J. Biol. Chem., 285 (2010), 56–64. https://doi.org/10.1074/jbc.M110.108209 doi: 10.1074/jbc.M110.108209
    [11] Z. Chen, M. C. Johnson, M. J. Chen, S. E. Boyken, B. Lin, D. Yoreo, et al., Self-assembling 2D arrays with de novo protein building blocks, J. Am. Chem. Soc., 141 (2019), 8891–8895. https://doi.org/10.1021/jacs.9b01978 doi: 10.1021/jacs.9b01978
    [12] J. Wang, T. Hou, Drug and drug candidate building block analysis, J. Chem. Inf. Model., 50 (2009), 55–67. https://doi.org/10.1021/ci900398f doi: 10.1021/ci900398f
    [13] N. Rong, C. Ying, Nano assembly of oligopeptides and DNA mimics the sequential disassembly of a spherical virus, Angew. Chem. Int. Edit., 59 (2020), 3578–3584. https://doi.org/10.1002/anie.201913611 doi: 10.1002/anie.201913611
    [14] Q. Chen, J. Gouilly, Y. J. Ferrat, A. Espino, N. J. Ferrat, Metabolic reprogramming by Zika virus provokes inflammation in human placenta, Nat. Commun., 11 (2020), 1–16. https://doi.org/10.1038/s41467-020-16754-z doi: 10.1038/s41467-020-16754-z
    [15] E. Klipp, R. Herwig, A. Kowald, C. Wierling, H. Lehrach, Systems Biology in Practice. Concepts, Implementation and Application, WILEY-VCH Verlag GmbH & Co. KGA, Weinheim, 2008.
    [16] J. Lei, Systems Biology, Modeling, Analysis, and Simulation, Springer, 2021.
    [17] A. Canada, P. Drabek, A. Fonda, Ordinary Differential Equations, Elsvier Science Ltd, 2006.
    [18] R. C. Dorf, R. H. Bishop, Modern Control Systems, Prentice Hall, 2008.
  • Reader Comments
  • © 2023 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(1409) PDF downloads(60) Cited by(1)

Article outline

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog