CR-I-TASSER: assemble protein structures from cryo-EM density maps using deep convolutional neural networks.

Abstract

Cryo-electron microscopy (cryo-EM) has become a leading approach for protein structure determination, but it remains challenging to accurately model atomic structures with cryo-EM density maps. We propose a hybrid method, CR-I-TASSER, which integrates deep neural-network learning with I-TASSER assembly simulations for automated cryo-EM structure determination. The method is benchmarked on 778 proteins with simulated and experimental density maps, where CR-I-TASSER constructs models with a correct fold (TM-score>0.5) for 643 targets that is 64% higher than the best of other de novo and refinement-based approaches on high-resolution data samples. Detailed data analyses showed that the major advantage of CR-I-TASSER lies in the deep-learning based position prediction, which significantly improves the threading template quality and therefore boosts the accuracy of final models through optimized fragment assembly simulations. These results demonstrate a new avenue to determine cryo-EM protein structures with high accuracy and robustness covering various target types and density-map resolutions.