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On Estimation of a Viral Protein Diffusion Constant on the Curved Intracellular ER Surface

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High Performance Computing in Science and Engineering ’15

Abstract

Advanced simulations within biophysical applications ask for advanced algorithms and implementations which are running efficiently on massively parallel high performance computers. The software framework UG fulfills these preconditions. Therefore, we present insight into the experimental basics, the modelling and simulation details, and the biophysical meaning of the estimation of the diffusion constant of a major player in the replication of the genetic information of the Hepatitis C virus (HCV), namely the NS5A viral protein. NS5A movement is restricted to the surface of the Endoplasmatic Reticulum (ER, a medusa-hair like important cell compartment). Hence, the dynamics of NS5A are described by surface PDEs (sPDE) which mimic experimental FRAP (fluorescence recovery after photobleaching) time series data. The sPDE computations were performed with UG upon large unstructured grids representing realistic reconstructed ER surfaces. We explain the context of the parameter estimations which asked for a substantial amount of single sPDE evaluations which we performed on the HLRS Stuttgart Hermit and Hornet supercomputers for various experimental data sets and for various geometric setups. This enabled us to derive valid final values for the diffusion constant of NS5A on the ER surface. The estimated diffusion constant values are intended to enter spatio-temporal resolved models of HCV replication dynamics at a cellular level.

The authors “E. Herrmann and G. Wittum” contributed equally.

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Notes

  1. 1.

    some geometries need more, some less, caused by the different node number of the reconstructed geometries.

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Acknowledgements

This work has been supported by the Goethe-Universität Frankfurt. We thank K. Xylouris (G-CSC) for very fruitful discussions on the evaluation of the simulation results, R. Dutta-Roy (Karolinska Institute, Stockholm, Sweden) for profound explanations of FRAP experimental setup and data analysis and Wouter van Beerendonk (Huygens SVI, Netherlands) for his very friendly support in Huygens usage, backgrounds, and licensing. The HLRS Stuttgart is acknowledged for the supplied computing time on the Hermit and Hornet supercomputers. John McLauchlan, Glasgow University, is acknowledged for providing the FRAP time series data [11] as experimental basis of the parameter estimation procedures.

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Authors and Affiliations

  1. Goethe-Center for Scientific Computing, Frankfurt University, Frankfurt, Germany

    M. M. Knodel

  2. Institute of Radiology, University Medical Center Erlangen, Erlangen, Germany

    M. M. Knodel

  3. Medivir AB, Department of Biology, Huddinge, Sweden

    M. Lampe & P. Targett-Adams

  4. Department of Medicine, Goethe University Frankfurt, Frankfurt, Germany

    E. Herrmann

Authors
  1. M. M. Knodel
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  2. A. Nägel
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  3. S. Reiter
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  4. M. Rupp
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  5. A. Vogel
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  6. M. Lampe
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  7. P. Targett-Adams
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  8. E. Herrmann
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  9. G. Wittum
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Corresponding author

Correspondence to M. Lampe .

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Editors and Affiliations

  1. Technische Universität Dresden, Dresden, Germany

    Wolfgang E. Nagel

  2. Abteilung für Angewandte Mathematik, Universität Freiburg, Freiburg, Germany

    Dietmar H. Kröner

  3. Höchstleistungsrechenzentrum, Universität Stuttgart, Stuttgart, Germany

    Michael M. Resch

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Knodel, M.M. et al. (2016). On Estimation of a Viral Protein Diffusion Constant on the Curved Intracellular ER Surface. In: Nagel, W., Kröner, D., Resch, M. (eds) High Performance Computing in Science and Engineering ’15. Springer, Cham. https://doi.org/10.1007/978-3-319-24633-8_41

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