Powder Diffraction Methods for Membrane Protein Structure Determination

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Membrane proteins comprise a large proportion of all the proteins coded by human and other eukaryotic genomes, and are the targets of more than one-half of all the pharmaceutical drugs marketed today. Knowledge of their three-dimensional structure is important for understanding how they function, and for the development of new drugs for the treatment of diseases. Protein X-ray crystallographic studies, which require well-ordered, large single crystals of the protein, provide such structural information. However, one of the major obstacles to membrane protein structure determinations currently is the ability to produce crystals of a size and quality suitable for single crystal studies. Although often many much smaller crystals can be produced, there has yet to be a method developed to utilise these for the determination of the structure of membrane proteins. The aim of this project is to develop both the methodology and tools necessary to determine the structure of membrane proteins based on samples not of single crystals, but of bunches of very small (microcrystals) using powder diffraction techniques.