Tools for Protein Crystallisation


Title: Tools for Protein Crystallisation
Status: Active
Funding Organization: European Union




Leader in charge: E. Sareidakis
Start Date: 01/03/2008
Duration: 48 months


Summary Knowledge of the structure of biological macromolecules, especially proteins, at the molecular level, is necessary to the understanding of the biochemical mechanisms on which life depends, but also to key biomedical applications, such as rational drug design. It is also crucial to the chemical industry, agricultural research and bionanotechnology. X-ray crystallography is the only current method that allows the elucidation of the structure of large macromolecules at high, even atomic (1 A and sometimes better) resolution, i.e. the atom-by-atom determination of their three-dimensional structures.

      In the long process of the structure determination of a biological macromolecule, crystallisation is considered to be the most difficult and intractable step. Programme TOPCRYST aims to develop new methodology, which will allow the fast and effective determination of conditions for the crystallisation of any given protein. It has been found that a technique known as Dual Polarisation Interferometry (DPI) allows to observe early-stage crystal nucleation in a protein solution during a dialysis experiment and to distinguish this from the alternatives states of either fully soluble protein or amorphous aggregation. This feature will allow the determination of crystallisation conditions, complementing the standard time-consuming and unreliable method of trying hundreds of potential conditions until hitting a correct one.

      TOPCRYST is an “Industry-Academia Partnerships and Pathways” project involving the exchange of expertise between an SME based in the U.K., Farfield Group Ltd., the coordinator, N.C.S.R. “DEMOKRITOS”, Institute of Physical Chemistry and the Faculty of Medicine, Imperial College London. Farfield has developed and is producing the DPI instrumentation, whereas the Laboratory of Structural and Supramolecular Chemistry of Demokritos and Imperial College provide expertise in biological crystallisation as well as the proteins that are used in the project.