MOTIVATION: Accurate contact predictions can be used for predicting the structure of proteins. Until recently these methods were limited to very big protein families, decreasing their utility. However, recent progress by combining direct coupling analysis with machine learning methods has made it possible to predict accurate contact maps for smaller families. To what extent these predictions can be used to produce accurate models of the families is not known. RESULTS: We present the PconsFold2 pipeline that uses contact predictions from PconsC3, the CONFOLD folding algorithm and model quality estimations to predict the structure of a protein. We show that the model quality estimation significantly increases the number of models that reliably can be identified. Finally, we apply PconsFold2 to 6379 Pfam families of unknown structure and find that PconsFold2 can, with an estimated 90% specificity, predict the structure of up to 558 Pfam families of unknown structure. Out of these, 415 have not been reported before. AVAILABILITY AND IMPLEMENTATION: Datasets as well as models of all the 558 Pfam families are available at http://c3.pcons.net/ . All programs used here are freely available. CONTACT: [email protected].

SUMMARY: Protein quality assessment is a long-standing problem in bioinformatics. For more than a decade we have developed state-of-art predictors by carefully selecting and optimising inputs to a machine learning method. The correlation has increased from 0.60 in ProQ to 0.81 in ProQ2 and 0.85 in ProQ3 mainly by adding a large set of carefully tuned descriptions of a protein. Here, we show that a substantial improvement can be obtained using exactly the same inputs as in ProQ2 or ProQ3 but replacing the support vector machine by a deep neural network. This improves the Pearson correlation to 0.90 (0.85 using ProQ2 input features). AVAILABILITY AND IMPLEMENTATION: ProQ3D is freely available both as a webserver and a stand-alone program at http://proq3.bioinfo.se/. CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Model quality assessment programs are used to predict the quality of modeled protein structures. They can be divided into two groups depending on the information they are using: ensemble methods using consensus of many alternative models and methods only using a single model to do its prediction. The consensus methods excel in achieving high correlations between prediction and true quality measures. However, they frequently fail to pick out the best possible model, nor can they be used to generate and score new structures. Single-model methods on the other hand do not have these inherent shortcomings and can be used both to sample new structures and to improve existing consensus methods. RESULTS: Here, we present an implementation of the ProQ2 program to estimate both local and global model accuracy as part of the Rosetta modeling suite. The current implementation does not only make it possible to run large batch runs locally, but it also opens up a whole new arena for conformational sampling using machine learned scoring functions and to incorporate model accuracy estimation in to various existing modeling schemes. ProQ2 participated in CASP11 and results from CASP11 are used to benchmark the current implementation. Based on results from CASP11 and CAMEO-QE, a continuous benchmark of quality estimation methods, it is clear that ProQ2 is the single-model method that performs best in both local and global model accuracy. AVAILABILITY AND IMPLEMENTATION: https://github.com/bjornwallner/ProQ_scripts CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.