Precise knowledge of the three dimensional (3D) structure of a given protein forms the basis of understanding its mechanism of action. Such knowledge is particularly important for designing and developing new drugs, but is also essential to understand the biology of humans and of other organisms. The HUGO-project has determined the complete human genome where the focus has now shifted from the DNA level to the structure and function of gene products at the protein level. An important method for protein structure determination is X-ray crystallography. The method requires access to single protein crystals, which has been the primary limiting step. This project aims to complete development of LEVMAC, a piece of equipment used in the field of Proteomics - to assist the crystallization of macromolecular structures, especially to resolve difficult cases where crystals of protein-ligand complexes are sought by the pharmaceutical industry. We will refine the prototype LEVMAC into an affordable and user-friendly instrument with good accuracy and validity, and with adequate software support. The LEVMAC device will be implemented in the frontline structural studies of naked and enveloped viruses, membrane receptor proteins, and protein-ligand complexes - areas in focus for advanced Proteomics and drug discovery. The equipment will allow structure determination of macromolecules to be reached faster and with higher accuracy than earlier, and at the same time waste less of precious macromolecular materials. To support these goals, the underlying algorithms for defining crystallization conditions will be further explored to provide nucleation phase diagrams. There is no competing equipment. Thus, the interest in the LEVMAC is expected to be very high among the pharmaceutical industries and within the scientific community. The proposed project will put CRAB at the forefront in the international Proteomics race and substantially benefit to the other participants as well.
Field of science
- /medical and health sciences/health sciences/infectious disease/RNA virus
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins/proteomics