Interactions between
biomacromolecules in solution are a key factor determining the
phase behavior of biological systems. Also, the phase
behavior determines whether one can get good quality protein
crystals for X-ray diffraction, which is critical in obtaining
the proteins three-dimensional structure and further to
elucidate its biochemical role. [1-3] On the other hand, the
protein interaction and aggregation processes are also very
important in understanding many physiological problems, for
example, diseases like Alzheimer or Kreutzfeld-Jacob and
Parkinson, which are caused by protein or peptide association
phenomena. Among the various factors, the electrostatic
effects play a major role in protein structure, interactions,
and dynamics. They depend on the protein itself, the
surrounding water, and ions present (see detail). This project addresses the important question of
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To answer these questions, the density and location of ions
around the protein, their specific interaction with surface
charges and the dynamics of these ions and the solvent will be
determined. These effects influence protein-protein
aggregation, the stability of protein-protein complexes, and
flexibility of individual protein side chains or whole loop
regions. |
By the combination of theoretical and experimental studies we gain a comprehensive picture of charge effects in this context. [11,12] The techniques complement each other, revealing a number of different aspects of charge effects. Experimentally, optical microscopy (view real-time video), spectroscopic lab-based techniques (IR, UV/vis, CD) as well as neutron and synchrotron-based scattering techniques (SAXS, ASAXS, QENS) are employed to determine the structure, the salt-ion distribution, and various aspects of the dynamics of individual proteins and protein complexes. Theoretical studies based on local and nonlocal continuum electrostatics calculations and molecular dynamics simulations complement the spectroscopic techniques. These techniques reveal counter ion distribution, the effect of ions on electrostatic shielding and molecular recognition, counter ion mobility and the influence of charge on local protein motion at atomic resolution. Approximate phase diagram of the interaction as a function of protein concentration and ionic strength. Note that the boundaries are, of course, not thought to be sharp. In the map, "Ellipsoidal" means the data were fitted by a form factor only. E+SC: data fitting by an ellipsoidal forma factor combined with a screened Coulombic structure factor. E+SW: ellipsoidal form factor combined with square-well structure factor. |
Currently, we are interested in the following issues:
[1] Durbin, S. D.; Feher, G. Annu. Rev. Phys. Chem. 1996, 47, 171.
[2] Anderson, V. J.; Lekkerkerker, H. N. W. Nature 2002, 416, 811.
[3] Piazza, R.; Curr. Opin. Colloid Interface Sci. 2004, 8, 515.
[4] George, A.; Wilson, W. Acta Cryst. 1994, D50, 361.
[5] Tardieu, A.; Le Verge, A.; Malfois, M.; Bonneté, F.; Finet, S.; Riès-
Kautt, M.; Belloni, L. J. Cryst. Growth 1999, 196, 193.
[6] Bonneté, F.; Finet, S.; Tardieu, A. J. Cryst. Growth 1999, 196, 403.
[7] Stradner, A.; Sedgwich, H.; Cardinaux, F.; Poon, W. C. K.; Egelhaaf, S.
U.; Schurtenberger, P. Nature 2004, 432, 492.
[8] Delaye, M.; Tardieu, A. Nature 1983, 302, 415.
[9] Curtis, R. A.; Prausnitz, J. M.; Blanch, H. W. Biotechnol. Bioeng. 1998,
57, 11.
[10] Collins, K. D. Biophys. J. 1997, 72, 65, Collins, K. D.; Washabaugh, M.
W. Q. Rev. Biophys. 1985, 18, 323
[11] F. Zhang, M.W.A. Skoda, R.M.J. Jacobs, R.A. Martin, C.M. Martin, F.
Schreiber, J. Phys. Chem. B, 111, 251 (2007)
[12] F. Zhang, M.W.A. Skoda, R.M.J. Jacobs, S. Zorn, R.A.
Martin, C.M. Martin, G. F. Clark, S. Weggler, A. Hildebrandt,
O. Kohlbacher, F. Schreiber, Phys. Rev. Lett. 101 (2008) 148101
For our recent work on proteins in solution, see list of publications.