One major obstacle to membrane protein structure determination is the selection of a detergent micelle that mimics the native lipid bilayer. Currently, detergents are selected by exhaustive screening because the effects of protein-detergent interactions on protein structure are poorly understood. Unlike lipids which form a bilayer, detergents form micelles. Micelles have different shapes and sizes depending on the detergent chemical structure. For NMR structural investigations, a multitude of detergents is screened until a condition that provides high quality NMR spectra is found. However, a correlation between the physical properties of the detergent micelle and the likelihood of obtaining a membrane protein structure is not known. The Columbus group is interested in studying how detergent – protein interactions modulate structure and dynamics and therefore structure determination of membrane proteins. Figure 3 shows three models of how three different detergent micelles could interact with the same model membrane protein.

Figure 3. A model demonstrating the hydrophobic matching between the surface area of the protein and different detergent shapes and sizes. The hydrophobic regions of the protein for which NOEs between the amide proton and the alkyl chain of detergent molecules were observed are colored red. Approximately 25% of the detergent micelle is removed in order to view the protein and the interior of the micelle.