Interactions of Polymers with Proteins.
Polymer Structure Database
J. Hašek1, J.
Dolinár, T. Skálová1, J. Dušková1, A. Štěpánková1,
T. Koval2, J. Dohnálek1
1 Institute of Macromolecular Chemistry AV ČR, Heyrovského nám.2, 16206 Praha 6,
2
hasek@imc.cas.cz
The currently available sources of
experimentally determined molecular structures are the “Cambridge Structure
Database of Organic and Organometalic Compounds (CSD)”
/1/ with 525 thousand structures, the “Protein Databank (PDB)” /2/ with 73500
structures and the “Polymer Structure Database (PolyBase)”
/3/ with 270 structures of polymers determined experimentally in solid state
and several thousands of “snapshots” of polymers built in the environment of
biological macromolecules. Non-commercial users in the Czech and
The review paper in /4/ summarizes the present status of the CSD. The example illustrating growing potential of the CSD with a rapidly growing number of molecular structures also shows the standing limits of accuracy and the limitations in quantitative verification of the empirical structure-function relations – here the σ- and/or π-bond electron-withdrawing or -donating effect caused by chemical substituents.
The second example is more relevant for this presentation. It shows that the knowledge contained in the CSD can be used to get information on polymer fragment interactions with other molecules. Comparing the information contained in the CSD, PDB and PolyBase, we can see a large variability of interactions and 3D structures formed by poly(oxyethylene type) polymers in different molecular environments. The basic features governing behavior of these polymers in biological environment, i.e. very specific adsorption on the protein surface were explained in /5/.
These special observations lead to formulation of a new theory providing a more rational way for protein crystal growth. The new concept of protein surface modifying agents (PSSA) and the principle of a single dominating interaction mode explained in /6/ promises an increase of diffraction quality, i.e. higher accuracy and reliability of protein structures. A large variability of different classes of the PSSA’s provides also a tool for crystallization of identical proteins in different space groups, i.e. it gives a chance to observe the structure of a protein in different molecular environments and with differently hydrated surface.
As far as the present status of the Polymer Structure Database (PolyBase) /3/, the search for deposited structures is now based on alphanumerical strings found in chemical names, trade marks or trivial names, i.e. on fragments found in any variant of the polymer name collected in the database. The user can choose any favorite programs for structure analysis; however the default tool for visual inspection of polymer structures in crystalline phase is now MERCURY 2.4.5 /7/. The default tool for inspection of adsorption of poly(oxyethylene) fragments on protein surface is the Protein Explorer /8/.
1. F. H. Allen, Acta Cryst., B58, 380-388, 2002 (www.ccdc.cam.ac.uk)
2. H.M. Berman et al, Nucleic Acids Res., 28, (2000), 235-242 (//ftp.wwpdb.org/pub/pdb/doc/newsletters/rcsb_pdb)
3. J. Hašek, Zeitschrift fur Kristallogr. 28 (2011), accepted.
4. J. Hašek, Chem. Listy 105, (2011), 467-475.
5. J. Hašek, Zeitschrift fur Kristallogr. 23, (2006), 613-619.
6. J. Hašek, J. Synchrotron Radiation, 18, (2011), 50-52.
7. C. F. Macrae, I. J. Bruno, J. A. Chisholm, P. R. Edgington, P. McCabe, E. Pidcock, L. Rodriguez-Monge, R. Taylor, J. van de Streek, P. A. Wood, J. Appl. Cryst., 41, (2008), 466-470. [DOI: 10.1107/S0021889807067908]
http://www.ccdc.cam.ac.uk/products/mercury/
8. http://www.pdb.org/pdb/staticHelp.do?p=help/viewers/ligandExplorer_viewer.html
The research is supported by grants
GA AV CR IAA500500701 and GA CR 305/07/1073