Improving Prediction of Protein Secondary Structure, Backbone Angles, Solvent Accessibility, and Contact Numbers by Using Predicted Contact Maps and an Ensemble of Recurrent and Residual Convolutional Neural Networks.

Motivation: Sequence-based prediction of one dimensional structural properties of proteins has been a long-standing subproblem of protein structure prediction. Recently, prediction accuracy has been significantly improved due to the rapid expansion of protein sequence and structure libraries and advances in deep learning techniques, such as residual convolutional networks (ResNets) and Long-Short-Term Memory Cells in Bidirectional Recurrent Neural Networks (LSTM-BRNNs). Here we leverage an ensemble of LSTM-BRNN and ResNet models, together with predicted residue-residue contact maps, to continue the push towards the attainable limit of prediction for 3- and 8-state secondary structure, backbone angles (θ, τ, ϕ, and ψ), half-sphere exposure, contact numbers, and solvent accessible surface area (ASA).

Results: The new method, named SPOT-1D, achieves similar, high performance on a large validation set and test set (≈1000 proteins in each set), suggesting robust performance for unseen data. For the large test set, it achieves 87% and 77% in 3 and 8-state secondary structure prediction and 0.82 and 0.86 in correlation coefficients between predicted and measured ASA and contact numbers, respectively. Comparison to current state-of-the-art techniques reveals substantial improvement in secondary structure and backbone angle prediction. In particular, 44% of 40-residue fragment structures constructed from predicted backbone Cα-based θ and τ angles are less than 6Å root-mean-squared-distance from their native conformations, nearly 20% better than the next best. The method is expected to be useful for advancing protein structure and function prediction.

Availability: SPOT-1D and its data is available at: https://sparks-lab.org/.

Supplementary Information: Supplementary data is available at Bioinformatics online.