Resolution Enhancement of Electron Microscopic Volume by Volume Restoration Technique

The knowledge of structure of proteins, protein derived compounds and RNA structures in eukaryotic cell is mandatory to understand the functions of these macromolecules.With recent development of Direct Electron Detector Device (DDD) camera and application of maximum likelihood algorithms in volume reconstruction,cryo Electron Microscopy (cryo-EM) enables us to visualize the macromolecules in nearly physiological state. The current resolution limit of cryo-EM can be improved further by applying novel and effective signal processing algorithms after the EM workflow. In this work, a signal processing method has been developed to enhance the resolution of the EM volume through volume restoration techniques. We have proposed a novel technique to estimate the volume degradation function of the volume reconstruction system from the noise-only subvolumes of the observed EM volume. Then the volume is restored (utilizing the estimated volume degradation function) using a combination of regularized Richardson-Lucy and Wiener Deconvolution techniques. In addition to volume restoration, we have employed spatial de-noising techniques utilizing various morphological filters to reduce noise outside the main molecular structure. The experimental results demonstrate that the resolution (evaluated by ourier Shell Correlation curve) and visual quality of the EM volume can be significantly improved using our proposed technique.