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One of the goals for the Membrane Protein Structural Biology Consortium (MPSBC) is to develop crystallization screens specifically tailored to transmembrane proteins (TMPs). This class of proteins presents a greater challenge, since they require an initial detergent solubilization step to remove the protein from the lipid bilayer of a membrane and form a stable, homogeneous, protein-detergent complex (PDC).  Subsequent crystallization of the PDC requires the manipulation of its dual surface properties in the presence of various precipitants.
Since membrane proteins have been observed to form crystals close to the phase boundaries of the detergent used in the crystallization experiment, knowledge of these boundaries under different precipitant conditions can serve as the foundation for the design of optimal crystallization screens for membrane proteins .
Beginning with dye-partitioning experiments that characterized the phase separation boundaries of pure detergents in the presence of various precipitants (Fig. 1), the Malkowski laboratory has generated and refined empirically derived detergent phase data that encompasses 11 detergents, 11 salts, and 10 polyethylene glycols (PEGs). These phase data have been made readily accessible through the creation of an Excel-based applet (SlickSpot) that allows an investigator to formulate crystallization cocktail grid screens containing PEGs and salts, specifically targeting regions near, but not beyond the phase partitioning boundaries of, the 11 detergents tested.
The phase data have also been used to formulate a TMP crystallization screen consisting of 1536 cocktails and to make it compatible with the liquid-handling robots and standard operating procedures used in the High-Throughput Crystallization Screening Laboratory at the Hauptman-Woodward Institute .
Beta testing of the 1536-experiment TMP screen was initiated with the acceptance of the first TMP samples in August 2008. As of March 2011, there have been more than 300 samples for about 175 unique macromolecules submitted to the TMP screen by the structural biology and structural genomics communities. The MPSBC staff modifies the cocktail list periodically in an attempt to increase the frequency of successful outcomes.
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