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Protein structure prediction has been greatly improved, but there are still a good portion of predicted models that do not have very high quality. Protein model refinement is one of the methods that may further improve model quality.Nevertheless, it is very challenging to refine a protein model towards better quality. Currently the most successful refinement methods rely on extensive conformation sampling and thus, take hours or days to refine even a single protein model. Here we propose a fast and effective method that may refine protein models with very limited conformation sampling. Our method applies GNN (graph neural networks) to predict refined inter-atom distance probability distribution from an initial model and then rebuilds the model using the predicted distance as restraints. On the CASP13 refinement targets our method may refine models with comparable quality as the two leading human groups (Feig and Baker) and greatly outperforms the others. On the CASP14 refinement targets our method is only second to Feig's method, comparable to Baker's method and much better than the others (who worsened instead of improved model quality). Our method achieves this result by generating only 5 refined models for an initial model, which can be done in ~15 minutes. Our study also shows that GNN performs much better than convolutional residual neural networks for protein model refinement when conformation sampling is limited.

As cancer remains one of the main threats of human life, developing efficient cancer treatments is urgent. Anticancer peptides, which could overcome the significant side effects and poor results of traditional cancer treatments, have become a new potential alternative these years. However, identifying anticancer peptides by experimental methods is time consuming and resource consuming, it is of great significance to develop effective computational tools to quickly and accurately identify potential anticancer peptides from amino acid sequences. For most current computational methods, feature representation plays a key role in their final successes. This study proposes a novel fast and accurate approach to identify anticancer peptides using diversified feature representations and ensemble learning method. For the feature representations, the information is encoded from multidimensional feature spaces, including sequence composition, sequence-order, physicochemical properties, etc. In order to better model the potential relationships of peptides, multiple ensemble classifiers, LightGBMs, are applied to detect the different feature sets at first. Then the obtained multiple outputs are used as inputs of the support vector machine classifier, which effectively identifies anticancer peptides. Experimental results on cross validation and independent test sets demonstrate that our method can achieve better or comparable performances compared with other state-of-the-art methods.

BackgroundProtein structure prediction has achieved a lot of progress during the last few decades and a greater number of models for a certain sequence can be predicted. Consequently, assessing the qualities of predicted protein models in perspective is one of the key components of successful protein structure prediction. Over the past years, a number of methods have been developed to address this issue, which could be roughly divided into three categories: single methods, quasi-single methods and clustering (or consensus) methods. Although these methods achieve much success at different levels, accurate protein model quality assessment is still an open problem.ResultsHere, we present the MQAPRank, a global protein model quality assessment program based on learning-to-rank. The MQAPRank first sorts the decoy models by using single method based on learning-to-rank algorithm to indicate their relative qualities for the target protein. And then it takes the first five models as references to predict the qualities of other models by using average GDT_TS scores between reference models and other models. Benchmarked on CASP11 and 3DRobot datasets, the MQAPRank achieved better performances than other leading protein model quality assessment methods. Recently, the MQAPRank participated in the CASP12 under the group name FDUBio and achieved the state-of-the-art performances.ConclusionsThe MQAPRank provides a convenient and powerful tool for protein model quality assessment with the state-of-the-art performances, it is useful for protein structure prediction and model quality assessment usages.

Motivation: Accurately estimating protein model quality in the absence of experimental structure is not only important for model evaluation and selection, but also useful for model refinement. Progress has been steadily made by introducing new features and algorithms (especially deep neural networks), but accuracy of quality assessment (QA) is still not very satisfactory, especially local QA on hard protein targets. Results: We propose a new single-model-based QA method ResNetQA for both local and global quality assessment. Our method predicts model quality by integrating sequential and pairwise features using a deep neural network composed of both 1D and 2D convolutional residual neural networks (ResNet). The 2D ResNet module extracts useful information from pairwise features such as model-derived distance maps, co-evolution information and predicted distance potential. The 1D ResNet is used to predict local (global) model quality from sequential features and pooled pairwise information generated by 2D ResNet. Tested on the CASP12 and CASP13 datasets, our experimental results show that our method greatly outperforms existing state-of-the-art methods. Our ablation studies indicate that the 2D ResNet module and pairwise features play an important role in improving model quality assessment. Availability and Implementation: https://github.com/AndersJing/ResNetQA

Much progress has been made in Protein structure prediction during the last few decades. As the predicted models can span a broad range of accuracy spectrum, the accuracy of quality estimation becomes one of the key elements of successful protein structure prediction. Over the past years, a number of methods have been developed to address this issue, and these methods could be roughly divided into three categories: the single-model methods, clustering-based methods and quasi single-model methods. In this study, we develop a single-model method MQAPRank based on the learning-to-rank algorithm firstly, and then implement a quasi single-model method Quasi-MQAPRank. The proposed methods are benchmarked on the 3DRobot and CASP11 dataset. The five-fold cross-validation on the 3DRobot dataset shows the proposed single model method outperforms other methods whose outputs are taken as features of the proposed method, and the quasi single-model method can further enhance the performance. On the CASP11 dataset, the proposed methods also perform well compared with other leading methods in corresponding categories. In particular, the Quasi-MQAPRank method achieves a considerable performance on the CASP11 Best150 dataset.

Motivation Accurately estimating protein model quality in the absence of experimental structure is not only important for model evaluation and selection but also useful for model refinement. Progress has been steadily made by introducing new features and algorithms (especially deep neural networks), but the accuracy of quality assessment (QA) is still not very satisfactory, especially local QA on hard protein targets. Results We propose a new single-model-based QA method ResNetQA for both local and global quality assessment. Our method predicts model quality by integrating sequential and pairwise features using a deep neural network composed of both 1D and 2D convolutional residual neural networks (ResNet). The 2D ResNet module extracts useful information from pairwise features such as model-derived distance maps, co-evolution information, and predicted distance potential from sequences. The 1D ResNet is used to predict local (global) model quality from sequential features and pooled pairwise information generated by 2D ResNet. Tested on the CASP12 and CASP13 datasets, our experimental results show that our method greatly outperforms existing state-of-the-art methods. Our ablation studies indicate that the 2D ResNet module and pairwise features play an important role in improving model quality assessment. Availability and implementation https://github.com/AndersJing/ResNetQA. Contact jinboxu@gmail.com Supplementary information Supplementary data are available at Bioinformatics online.

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