Improved Protein Structure Prediction Using a New Multi-Scale Network and Homologous Templates.

The accuracy of de novo protein structure prediction has been improved considerably in recent years, mostly due to the introduction of deep learning techniques. In this work, trRosettaX, an improved version of trRosetta for protein structure prediction is presented. The major improvement over trRosetta consists of two folds. The first is the application of a new multi-scale network, i.e., Res2Net, for improved prediction of inter-residue geometries, including distance and orientations. The second is an attention-based module to exploit multiple homologous templates to increase the accuracy further. Compared with trRosetta, trRosettaX improves the contact precision by 6% and 8% on the free modeling targets of CASP13 and CASP14, respectively. A preliminary version of trRosettaX is ranked as one of the top server groups in CASP14's blind test. Additional benchmark test on 161 targets from CAMEO (between Jun and Sep 2020) shows that trRosettaX achieves an average TM-score ≈0.8, outperforming the top groups in CAMEO. These data suggest the effectiveness of using the multi-scale network and the benefit of incorporating homologous templates into the network. The trRosettaX algorithm is incorporated into the trRosetta server since Nov 2020. The web server, the training and inference codes are available at: https://yanglab.nankai.edu.cn/trRosetta/.