Skip to main content
SpringerLink
Log in

The Internal Dynamics and Early Adsorption Stages of Fibrinogen Investigated by Molecular Dynamics Simulations

  • Conference paper
  • First Online:
High Performance Computing in Science and Engineering ´16

  • 1717 Accesses

Abstract

Fibrinogen, a plasma glycoprotein of vertebrates, plays an essential role in blood clotting by polymerizing into fibrin upon activation. It also contributes, upon adsorption on material surfaces, to determine their biocompatibility and has been implicated as a cause of thrombosis and inflammation at medical implants. Here we present the first fully atomistic simulations of the initial stages of the adsorption process of fibrinogen on mica and graphite surfaces. The simulations reveal a weak adsorption on mica that allows frequent desorption and reorientation events. This adsorption is driven by electrostatic interactions between the protein and the silicate surface as well as the counter ion layer. Preferred adsorption orientations for the globular regions of the protein are identified. The adsorption on graphite is found to be stronger with fewer reorientation and desorption events, and showing the onset of denaturation of the protein.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Weisel, J.W.: J. Thromb. Haemost. 5 (Suppl 1), 116 (2007). doi:10.1111/j.1538-7836.2007.02504.x. http://dx.doi.org/10.1111/j.1538-7836.2007.02504.x

    Article  Google Scholar 

  2. Takagi, T., Doolittle, R.F.: Biochemistry 14 (23), 5149 (1975). doi:10.1021/bi00694a020. http://dx.doi.org/10.1021/bi00694a020

    Article  Google Scholar 

  3. Takagi, T., Doolittle, R.F.: Biochemistry 14 (5), 940 (1975)

    Article  Google Scholar 

  4. Mihalyi, E.: Ann. N. Y. Acad. Sci. 408 (1), 60 (1983). doi:10.1111/j.1749-6632.1983.tb23234.x. http://dx.doi.org/10.1111/j.1749-6632.1983.tb23234.x

    Article  Google Scholar 

  5. Kollman, J., Pandi, L., Sawaya, M., Riley, M., Doolittle, R.: Biochemistry 48 (18), 3877 (2009). doi:10.1021/bi802205g. http://pubs.acs.org/doi/abs/10.1021/bi802205g

    Article  Google Scholar 

  6. Köhler, S., Schmid, F., Settanni, G.: PLoS Comput. Biol. 11 (9), e1004346 (2015). doi:10.1111/j.1538-7836.2007.02504.x. doi:10.1111/j.1538-7836.2007.02504.x

    Google Scholar 

  7. Altieri, D.C., Plescia, J., Plow, E.F.: J. Biol. Chem. 268 (3), 1847 (1993)

    Article  Google Scholar 

  8. Ugarova, T.P., Solovjov, D.A., Zhang, L., Loukinov, D.I., Yee, V.C., Medved, L.V., Plow, E.F.: J. Biol. Chem. 273 (35), 22519 (1998)

    Article  Google Scholar 

  9. Kloczewiak, M., Timmons, S., Hawiger, J.: Biochem. Biophys. Res. Commun. 107 (1), 181 (1982)

    Article  Google Scholar 

  10. Soman, P., Rice, Z., Siedlecki, C.A.: Langmuir 24 (16), 8801 (2008). doi:10.1021/la801227e. http://pubs.acs.org/doi/abs/10.1021/la801227e

    Article  Google Scholar 

  11. Yermolenko, I.S., Lishko, V.K., Ugarova, T.P., Magonov, S.N.: Biomacromolecules 12 (2), 370 (2011). doi:10.1021/bm101122g. http://pubs.acs.org/doi/abs/10.1021/bm101122g

    Article  Google Scholar 

  12. Protopopova, A.D., Barinov, N.A., Zavyalova, E.G., Kopylov, A.M., Sergienko, V.I., Klinov, D.V.: J. Thromb. Haemost. 13 (4), 570 (2015). doi:10.1111/jth.12785. http://dx.doi.org/10.1111/jth.12785

    Article  Google Scholar 

  13. Doolittle, R.F., Goldbaum, D.M., Doolittle, L.R.: J. Mol. Biol. 120 (2), 311 (1978). doi:http://dx.doi.org/10.1111/j.1749-6632.1983.tb23234.x. http://www.sciencedirect.com/science/article/pii/0022283678900700

  14. Brown, J.H., Volkmann, N., Jun, G., Henschen-Edman, A.H., Cohen, C.: Proc. Natl. Acad. Sci. U. S. A. 97 (1), 85 (2000). doi:10.1073/pnas.97.1.85. http://www.pnas.org/content/97/1/85.abstract

  15. Yang, Z., Kollman, J.M., Pandi, L., Doolittle, R.F.: Biochemistry 40 (42), 12515 (2001)

    Article  Google Scholar 

  16. Beijbom, L., Larsson, U., Kaveus, U., Hebert, H.: J. Ultrastruct. Mol. Struct. Res. 98 (3), 312 (1988). doi:10.1016/S0889-1605(88)80923-6. http://www.sciencedirect.com/science/article/pii/S0889160588809236

    Article  Google Scholar 

  17. Marchin, K.L., Berrie, C.L.: Langmuir 19 (23), 9883 (2003). doi:10.1021/la035127r. http://pubs.acs.org/doi/abs/10.1021/la035127r

    Article  Google Scholar 

  18. Tunc, S., Maitz, M.F., Steiner, G., Vazquez, L., Pham, M.T., Salzer, R.: Colloids Surf. B 42 (3–4), 219 (2005). doi:10.1016/j.colsurfb.2005.03.004. http://www.sciencedirect.com/science/article/pii/S0927776505000986

    Article  Google Scholar 

  19. Sit, P., Marchant, R.E.: Surf. Sci. 491 (3), 421 (2001). doi:10.1016/S0039-6028(01)01308-5. http://www.sciencedirect.com/science/article/pii/S0039602801013085

    Article  Google Scholar 

  20. Agnihotri, A., Siedlecki, C.A.: Langmuir 20 (20), 8846 (2004). doi:10.1021/la049239+. http://pubs.acs.org/doi/abs/10.1021/la049239%2B

    Article  Google Scholar 

  21. Heinz, H.: J. Comput. Chem. 31 (7), 1564 (2010). doi:10.1002/jcc.21421. http://dx.doi.org/10.1002/jcc.21421

    Article  Google Scholar 

  22. Starzyk, A., Cieplak, M.: J. Chem. Phys. 139 (4), 045102 (2013). doi:10.1063/1.4813854. http://dx.doi.org/10.1063/1.4813854

    Article  Google Scholar 

  23. Kubiak-Ossowska, K., Burley, G., Patwardhan, S.V., Mulheran, P.A.: J. Phys. Chem. B 117 (47), 14666 (2013). doi:10.1021/jp409130s. http://dx.doi.org/10.1021/jp409130s

    Article  Google Scholar 

  24. Raffaini, G., Ganazzoli, F.: Langmuir 19 (8), 3403 (2003). doi:10.1021/la026853h. http://pubs.acs.org/doi/abs/10.1021/la026853h

    Article  Google Scholar 

  25. Utesch, T., Daminelli, G., Mroginski, M.A.: Langmuir 27 (21), 13144 (2011). doi:10.1021/la202489w. http://pubs.acs.org/doi/abs/10.1021/la202489w

    Article  Google Scholar 

  26. Kang, S.G., Huynh, T., Xia, Z., Zhang, Y., Fang, H., Wei, G., Zhou, R.: J. Am. Chem. Soc. 135 (8), 3150 (2013). doi:10.1021/ja310989u. http://pubs.acs.org/doi/abs/10.1021/ja310989u

    Article  Google Scholar 

  27. Baweja, L., Balamurugan, K., Subramanian, V., Dhawan, A.: Langmuir 29 (46), 14230 (2013). doi:10.1021/la4033805. http://dx.doi.org/10.1021/la4033805

    Article  Google Scholar 

  28. Chong, Y., Ge, C., Yang, Z., Garate, J.A., Gu, Z., Weber, J.K., Liu, J., Zhou, R.: ACS Nano 9 (6), 5713 (2015). doi:10.1021/nn5066606. http://dx.doi.org/10.1021/nn5066606

    Article  Google Scholar 

  29. Agashe, M., Raut, V., Stuart, S.J., Latour, R.A.: Langmuir 21 (3), 1103 (2005). doi:10.1021/la0478346. http://pubs.acs.org/doi/abs/10.1021/la0478346

    Article  Google Scholar 

  30. Lim, B.B., Lee, E.H., Sotomayor, M., Schulten, K.: Structure 16 (3), 449 (2008). doi:10.1016/j.str.2007.12.019. http://www.sciencedirect.com/science/article/pii/S0969212608000476

    Article  Google Scholar 

  31. Zhmurov, A., Brown, A.E., Litvinov, R.I., Dima, R.I., Weisel, J.W., Barsegov, V.: Structure 19 (11), 1615 (2011). doi:10.1016/j.str.2011.08.013

    Article  Google Scholar 

  32. Adamczyk, Z., Barbasz, J., Cieśla, M.: Langmuir 26 (14), 11934 (2010). doi:10.1021/la101261f. http://pubs.acs.org/doi/abs/10.1021/la101261f

    Article  Google Scholar 

  33. Adamczyk, Z., Barbasz, J., Cieśla, M.: Langmuir 27 (11), 6868 (2011). doi:10.1021/la200798d. http://pubs.acs.org/doi/abs/10.1021/la200798d

    Article  Google Scholar 

  34. Vilaseca, P., Dawson, K.A., Franzese, G.: Soft Matter 9, 6978 (2013). doi:10.1039/C3SM50220A. http://dx.doi.org/10.1039/C3SM50220A

    Article  Google Scholar 

  35. Rocco, M., Molteni, M., Ponassi, M., Giachi, G., Frediani, M., Koutsioubas, A., Profumo, A., Trevarin, D., Cardinali, B., Vachette, P., Ferri, F., Prez, J.: J. Am. Chem. Soc. 136 (14), 5376 (2014). doi:10.1021/ja5002955. http://dx.doi.org/10.1021/ja5002955

    Article  Google Scholar 

  36. Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W., Klein, M.L.: J. Chem. Phys. 79 (2), 926 (1983). doi:10.1063/1.445869. http://link.aip.org/link/?JCP/79/926/1

    Article  Google Scholar 

  37. Humphrey, W., Dalke, A., Schulten, K.: J. Mol. Graph. 14, 33 (1996)

    Article  Google Scholar 

  38. Phillips, J.C., Braun, R., Wang, W., Gumbart, J., Villa, E., Chipot, C., Skeel, R.D., Kale, L., Schulten, K.: J. Comput. Chem. 26, 1781 (2005)

    Article  Google Scholar 

  39. Martyna, G.J., Tobias, D.J., Klein, M.L.: J. Chem. Phys. 101 (5), 4177 (1994). doi:10.1063/1.467468. http://link.aip.org/link/?JCP/101/4177/1

    Article  Google Scholar 

  40. Feller, S.E., Zhang, Y., Pastor, R.W., Brooks, B.R.: J. Chem. Phys. 103 (11), 4613 (1995). doi:10.1063/1.470648. http://link.aip.org/link/?JCP/103/4613/1

    Article  Google Scholar 

  41. Mackerell, A.D., Feig, M., Brooks, C.L.: J. Comput. Chem. 25 (11), 1400 (2004). doi:10.1002/jcc.20065. http://dx.doi.org/10.1002/jcc.20065

    Article  Google Scholar 

  42. Guvench, O., Mallajosyula, S.S., Raman, E.P., Hatcher, E., Vanommeslaeghe, K., Foster, T.J., Jamison, F.W., MacKerell, A.D.: J. Chem. Theory Comput. 7 (10), 3162 (2011). doi:10.1021/ct200328p. http://pubs.acs.org/doi/abs/10.1021/ct200328p

    Article  Google Scholar 

  43. Vanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S., Zhong, S., Shim, J., Darian, E., Guvench, O., Lopes, P., Vorobyov, I., Mackerell, A.D.: J. Comput. Chem. 31 (4), 671 (2010). doi:10.1002/jcc.21367. http://dx.doi.org/10.1002/jcc.21367

    Article  Google Scholar 

  44. Heinz, H., Koerner, H., Anderson, K.L., Vaia, R.A., Farmer, B.L.: Chem. Mater. 17 (23), 5658 (2005). doi:10.1021/cm0509328. http://pubs.acs.org/doi/abs/10.1021/cm0509328

    Article  Google Scholar 

  45. Bertran, O., Curcó, D., Zanuy, D., Alemán, C.: Faraday Discuss 166, 59 (2013)

    Article  Google Scholar 

  46. Maity, S., Zanuy, D., Razvag, Y., Das, P., Alemn, C., Reches, M.: Phys. Chem. Chem. Phys. 17 (23), 15305 (2015). doi:10.1039/c5cp00088b. http://dx.doi.org/10.1039/c5cp00088b

    Article  Google Scholar 

  47. Kitao, A., Hirata, F., Go, N.: Chem. Phys. 158, 447 (1991). doi:http://dx.doi.org/10.1016/0301-0104(91)87082-7. http://www.sciencedirect.com/science/article/pii/0301010491870827

    Article  Google Scholar 

  48. Seeber, M., Cecchini, M., Rao, F., Settanni, G., Caflisch, A.: Bioinformatics 23 (19), 2625 (2007)

    Article  Google Scholar 

  49. Spoel, D.V.D., Lindahl, E., Hess, B., Groenhof, G., Mark, A.E., Berendsen, H.J.C.: J. Comput. Chem. 26 (16), 1701 (2005). doi:10.1002/jcc.20291. http://dx.doi.org/10.1002/jcc.20291

    Article  Google Scholar 

  50. Poornam, G.P., Matsumoto, A., Ishida, H., Hayward, S.: Proteins: Struct. Funct. Bioinf. 76 (1), 201 (2009). doi:10.1002/prot.22339. http://dx.doi.org/10.1002/prot.22339

    Article  Google Scholar 

  51. Hess, B.: Phys. Rev. E. 62, 8438 (2000). doi:10.1103/PhysRevE.62.8438. http://link.aps.org/doi/10.1103/PhysRevE.62.8438

    Article  Google Scholar 

  52. Marsh, J.J., Guan, H.S., Li, S., Chiles, P.G., Tran, D., Morris, T.A.: Biochemistry 52 (32), 5491 (2013). doi:10.1021/bi4007995. http://pubs.acs.org/doi/abs/10.1021/bi4007995

    Article  Google Scholar 

  53. Linding, R., Jensen, L.J., Diella, F., Bork, P., Gibson, T.J., Russell, R.B.: Structure 11 (11), 1453 (2003). doi:http://dx.doi.org/10.1016/j.str.2003.10.002. http://www.sciencedirect.com/science/article/pii/S0969212603002351

  54. Weisel, J.W., Nagaswami, C., Makowski, L.: Proc. Natl. Acad. Sci. U. S. A. 84 (24), 8991 (1987)

    Google Scholar 

  55. Varj, I., Stonyi, P., Machovich, R., Szab, L., Tenekedjiev, K., Silva, M.M.C.G., Longstaff, C., Kolev, K.: J. Thromb. Haemost. 9 (5), 979 (2011). doi:10.1111/j.1538-7836.2011.04203.x. http://dx.doi.org/10.1111/j.1538-7836.2011.04203.x

    Article  Google Scholar 

  56. Yermolenko, I.S., Fuhrmann, A., Magonov, S.N., Lishko, V.K., Oshkadyerov, S.P., Ros, R., Ugarova, T.P.: Langmuir 26 (22), 17269 (2010). doi:10.1021/la101791r. http://pubs.acs.org/doi/abs/10.1021/la101791r

    Article  Google Scholar 

  57. Podolnikova, N.P., Yermolenko, I.S., Fuhrmann, A., Lishko, V.K., Magonov, S., Bowen, B., Enderlein, J., Podolnikov, A.V., Ros, R., Ugarova, T.P.: Biochemistry 49 (1), 68 (2010). doi:10.1021/bi9016022. http://pubs.acs.org/doi/abs/10.1021/bi9016022

    Article  Google Scholar 

  58. Patwardhan, S.V., Emami, F.S., Berry, R.J., Jones, S.E., Naik, R.R., Deschaume, O., Heinz, H., Perry, C.C.: J. Am. Chem. Soc. 134 (14), 6244 (2012). doi:10.1021/ja211307u. http://pubs.acs.org/doi/abs/10.1021/ja211307u

    Article  Google Scholar 

  59. Sivaraman, B., Latour, R.A.: Biomaterials 31 (5), 832 (2010). doi:10.1016/ j.biomaterials.2009.10.008. http://dx.doi.org/10.1016/j.biomaterials.2009.10.008

  60. Köhler, S., Schmid, F., Settanni, G.: Langmuir 31 (48), 13180–13190 (2015). doi:10.1021/acs.langmuir.5b03371. PMID: 26569042. http://dx.doi.org/10.1021/acs.langmuir.5b03371.

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank Prof. H. Heinz for providing the structure of the mica surface and for helpful discussions. SK gratefully acknowledges financial support from the Graduate School Materials Science in Mainz. GS gratefully acknowledges financial support from the Max-Planck Graduate Center with the University of Mainz. We gratefully acknowledge support with computing time from the HPC facility Mogon at the university of Mainz, the Jülich Supercomputing Center and the High performance computing center Stuttgart. This work was partially supported by the German Science Foundation within SFB 1066 (project Q1).

Author information

Authors and Affiliations

  1. Institut für Physik, Johannes Gutenberg University, Mainz, Germany

    Stephan Köhler, Friederike Schmid & Giovanni Settanni

Authors
  1. Stephan Köhler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Friederike Schmid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giovanni Settanni
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Zentrum für Informationsdienste und Hochleistungsrechnen (ZIH), Technische Universität Dresden, Dresden, Germany

    Wolfgang E. Nagel

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

    Dietmar H. Kröner

  3. Höchstleistungsrechenzentrum Stuttgart (HLRS), Universität Stuttgart, Stuttgart, Germany

    Michael M. Resch

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing AG

About this paper

Cite this paper

Köhler, S., Schmid, F., Settanni, G. (2016). The Internal Dynamics and Early Adsorption Stages of Fibrinogen Investigated by Molecular Dynamics Simulations. In: Nagel, W.E., Kröner, D.H., Resch, M.M. (eds) High Performance Computing in Science and Engineering ´16. Springer, Cham. https://doi.org/10.1007/978-3-319-47066-5_5

Download citation

Publish with us

Policies and ethics

Search

Navigation