Alpha helical membrane proteins are the targets for many pharmaceutical drugs and play important roles in physiology and disease processes. In recent years substantial progress has been made in determining their atomic structure using X-ray crystallography. However, a major bottleneck still remains; the identification of conditions that give crystals that are suitable for structure determination. Over the past 10 years we have been analyzing the crystallization conditions reported for alpha helical membrane proteins with the aim to facilitate a rational approach to the design and implementation of successful crystallization screens.
The result has been the development of MemGold, MemGold2, MemPlus and the additive screen MemAdvantage. The associated analysis, summarized and updated in this chapter, has revealed a number of surprisingly successfully strategies for crystallization and detergent selection.
The development of new methods to determine the crystal structures of membrane proteins is also an important part of our research. In addition to work in developing expression and screening technologies to identify suitable targets for biophysical study, we are also data mining the Protein Data Bank (PDB) to uncover emerging trends in alpha helical membrane protein crystallization.
Our latest screens, MemChannel and MemTrans are designed specifically to target channel and transporters respectively. These are now available from Molecular Dimensions Ltd. An LCP version of our popular MemGold range, MemGoldmeso is in the works and will be released soon.