Deep learning geometrical potential for high-accuracy ab initio protein structure prediction

Ab initio protein structure prediction has been vastly boosted by the modeling of inter-residue contact/distance maps in recent years. We developed a new deep learning model, DeepPotential, which accurately predicts the distribution of a complementary set of geometric descriptors including a novel hydrogen-bonding potential defined by C-alpha atom coordinates. On 154 Free-Modeling/Hard targets from the CASP and CAMEO experiments, DeepPotential demonstrated significant advantage on both geometrical feature prediction and full-length structure construction, with Top-L/5 contact accuracy and TM-score of full-length models 4.1% and 6.7% higher than the best of other deep-learning restraint prediction approaches. Detail analyses showed that the major contributions to the TM-score/contact-map improvements come from the employment of multi-tasking network architecture and metagenome-based MSA collection assisted with confidence-based MSA selection, where hydrogen-bonding and inter-residue orientation predictions help improve hydrogen-bonding network and secondary structure packing. These results demonstrated new progress in the deep-learning restraint-guided ab initio protein structure prediction.