We are developing novel computational methods to membrane protein structure determination that exploit and combine diverse data collection strategies.
Obtaining flat, distortion-free 2D crystals for high-resolution electron crystallography is a very difficult task. In order to make the sample quality requirements more amenable, we are introducing state-of-the-art single particle refinement techniques into structure determination 2D electron crystallography. By treating each unit cell as an individual particle, and exploiting its neighborhood correlations within the 2D crystal, it is possible to obtain a more flexible unbending of the crystal while also maintaining a relatively high SNR. With this approach, we hope to make electron crystallography a suitable technique for a broader range of proteins.