Determining Protein Secondary Structures in Heterogeneous Medium-Resolution Cryo-EM Images Using CryoSSESeg

While the acquisition of cryo-electron microscopy (cryo-EM) at near-atomic resolution is becoming more prevalent, a considerable number of density maps are still resolved only at intermediate resolutions (5-10 Å). Due to the large variation in quality among these medium-resolution density maps, extracting structural information from them remains a challenging task. This study introduces a convolutional neural network (CNN)-based framework, cryoSSESeg, to determine the organization of protein secondary structure elements in medium-resolution cryo-EM images. CryoSSESeg is trained on approximately 1300 protein chains derived from around 500 experimental cryo-EM density maps of varied quality. It demonstrates strong performance with residue-level F ₁ scores of 0.76 for helix detection and 0.60 for β-sheet detection on average across a set of testing chains. In comparison to traditional image processing tools like SSETracer, which demand significant manual intervention and preprocessing steps, cryoSSESeg demonstrates comparable or superior performance. Additionally, it demonstrates competitive performance alongside another deep learning-based model, Emap2sec. Furthermore, this study underscores the importance of secondary structure quality, particularly adherence to expected shapes, in detection performance, emphasizing the necessity for careful evaluation of the data quality.