Direct prediction of protein structure from sequence is a challenging problem. An effective approach is to break it up into independent sub-problems. These sub-problems such as prediction of protein secondary structure can then be solved independently. In a previous study, we found that an iterative use of predicted secondary structure and backbone torsion angles can further improve secondary structure and torsion angle prediction. In this study, we expand the iterative features to include solvent accessible surface area and backbone angles and dihedrals based on Cα atoms. By using a deep learning neural network in three iterations, we achieved 82% accuracy for secondary structure prediction, 0.76 for the correlation coefficient between predicted and actual solvent accessible surface area, 19° and 30° for mean absolute errors of backbone φ and ψ angles, respectively, and 8° and 32° for mean absolute errors of Cα-based θ and τ angles, respectively, for an independent test dataset of 1199 proteins. The accuracy of the method is slightly lower for 72 CASP 11 targets but much higher than those of model structures from current state-of-the-art techniques. This suggests the potentially beneficial use of these predicted properties for model assessment and ranking.
Because a nearly constant distance between two neighbouring Cα atoms, local backbone structure of proteins can be represented accurately by the angle between C(αi-1)-C(αi)-C(αi+1) (θ) and a dihedral angle rotated about the C(αi)-C(αi+1) bond (τ). θ and τ angles, as the representative of structural properties of three to four amino-acid residues, offer a description of backbone conformations that is complementary to φ and ψ angles (single residue) and secondary structures (>3 residues). Here, we report the first machine-learning technique for sequence-based prediction of θ and τ angles. Predicted angles based on an independent test have a mean absolute error of 9° for θ and 34° for τ with a distribution on the θ-τ plane close to that of native values. The average root-mean-square distance of 10-residue fragment structures constructed from predicted θ and τ angles is only 1.9Å from their corresponding native structures. Predicted θ and τ angles are expected to be complementary to predicted ϕ and ψ angles and secondary structures for using in model validation and template-based as well as template-free structure prediction. The deep neural network learning technique is available as an on-line server called Structural Property prediction with Integrated DEep neuRal network (SPIDER) at http://sparks-lab.org.
Predicting protein structure from sequence alone is challenging. Thus, the majority of methods for protein structure prediction rely on evolutionary information from multiple sequence alignments. In previous work we showed that Long Short-Term Bidirectional Recurrent Neural Networks (LSTM-BRNNs) improved over regular neural networks by better capturing intra-sequence dependencies. Here we show a single-sequence-based prediction method employing LSTM-BRNNs (SPIDER3-Single), that consistently achieves Q3 accuracy of 72.5%, and correlation coefficient of 0.67 between predicted and actual solvent accessible surface area. Moreover, it yields reasonably accurate prediction of eight-state secondary structure, main-chain angles (backbone ϕ and ψ torsion angles and Cα-atom-based θ and τ angles), half-sphere exposure, and contact number. The method is more accurate than the corresponding evolutionary-based method for proteins with few sequence homologs, and computationally efficient for large-scale screening of protein-structural properties. It is available as an option in the SPIDER3 server, and a standalone version for download, at http://sparks-lab.org.
Predicting one-dimensional structure properties has played an important role to improve prediction of protein three-dimensional structures and functions. The most commonly predicted properties are secondary structure and accessible surface area (ASA) representing local and nonlocal structural characteristics, respectively. Secondary structure prediction is further complemented by prediction of continuous main-chain torsional angles. Here we describe a newly developed method SPIDER2 that utilizes three iterations of deep learning neural networks to improve the prediction accuracy of several structural properties simultaneously. For an independent test set of 1199 proteins SPIDER2 achieves 82 % accuracy for secondary structure prediction, 0.76 for the correlation coefficient between predicted and actual solvent accessible surface area, 19° and 30° for mean absolute errors of backbone φ and ψ angles, respectively, and 8° and 32° for mean absolute errors of Cα-based θ and τ angles, respectively. The method provides state-of-the-art, all-in-one accurate prediction of local structure and solvent accessible surface area. The method is implemented, as a webserver along with a standalone package that are available in our website: http://sparks-lab.org .
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