Gradient based refinement of CryoET tilt series alignment improves tomogram contrast and structure resolution

Cryogenic electron tomography (CryoET) provides 3D views of vitrified cellular samples, and protein structures can be determined from the tomograms by averaging many copies of the same protein computationally. However, the resolution of these averaged structures, particularly for smaller proteins, is often constrained by the precision of tilt-series alignment. In this study, we introduce a gradient descent-based approach to refine alignment parameters, enhancing the contrast in tomograms of the sample regions. This refinement not only improves contrast but also yields higher-resolution protein structures derived from the same particle populations.