A Platform for Studying Structures of Membrane Proteins Inserted into Nanodiscs

Membrane proteins are critical to many biological processes and account for 70% of all know pharmacological targets. However, there are only a few hundred unique membrane protein structures available in protein data bank due to the difficulty in forming crystals for x-ray crystallography or electron crystallography. Several methods have been developed to study structures of membrane proteins in lipid membrane environments (e.g. helical, planar, or spherical membranes). Among those, insertion of membrane proteins in lipid nanodiscs offers some benefits in terms of size, homogeneity, and curvature. In the studied structures, the nanodisc is considered part of the whole complex. Here, we proposed to develop a platform to computationally remove the nanodisc contributions. This is essential for the proteins not inserted at a fixed position in nanodisc (i.e. proteins are floating in the nanodisc). In addition, the geometry of the nanodisc will be used to aid the determination of two of the three Euler angles. This will decrease the computational requirement, increase accuracy of the determined orientation of each individual protein particles, and thus increase the resolution of the determined structure.