Session Speaker

Prediction of Volume, Surface, and Hydration Properties of Proteins and Other Biomolecules
Helmut Durchschlag and Peter Zipper
Germany

High-resolution techniques provide information on the precise 3D structure of proteins or other biomacromolecules and bound water molecules; in general, however, only a maximum of one third of preferentially bound water molecules has been identified by crystallographic techniques. By contrast, data from low-resolution solution techniques inherently contain hydration [1, 2]. Hydration details, however, are required for understanding various biomacromolecule interactions in context of drug-design projects, construction of tailor-made proteins, and development of functionalized surfaces and polymers by mimicking biomacromolecules.

Volume, surface and hydration properties of low-molecular ligands (e.g. substrates, inhibitors, drugs) and biomacromolecules (e.g., simple and conjugated proteins, nucleic acids, macromolecule-ligand complexes) can be obtained by experimental techniques and calculative approaches as well, provided several problems and pitfalls are considered. Sequence and crystallographic data of macromolecules and ligands may be used as database, to predict molecular volumes, molecular surfaces, and the presumable position of individual water molecules preferentially bound to certain (amino acid) residues (obtained by applying our novel hydration algorithms: programs HYDCRYST and HYDMODEL) [2-5]. The good agreement of the results found for hydrated protein models by crystallography and other techniques offers the possibility to complement different techniques and to predict details such as the localization of potential water sites - even in those cases where no crystallographic waters or water channels have been identified.

Examples presented include proteins ranging from simple proteins to complex, multisubunit, liganded proteins in the MDa range, and other biomacromolecules as well. In this context, a variety of special applications can be mentioned: visualization of protein sites of special concern (charged, hydrophilic and hydrophobic residues and patches, docking sites and contact areas, individual waters, water clusters and water channels, position of crevices, channels of different width, etc.).

[1] H. Durchschlag, P. Zipper, and A. Krebs, J. Appl. Cryst. 40 (2007) 1123-1134.
[2] H. Durchschlag and P. Zipper, in: Analytical Ultracentrifugation: Techniques and Methods (D.J. Scott et al., eds.) Royal Society of Chemistry, Cambridge, 2005, pp. 389-431.
[3] H. Durchschlag and P. Zipper, J. Phys.: Condens. Matter 14 (2002) 2439-2452.
[4] H. Durchschlag and P. Zipper, Prog. Colloid Polymer Sci. 134 (2008) 19-29.
[5] P. Zipper and H. Durchschlag, Eur. Biophys. J. (2009) in press.