CASP (critical assessment of structure prediction) assesses the state of the art in modeling protein structure from amino acid sequence. The most recent experiment (CASP13 held in 2018) saw dramatic progress in structure modeling without use of structural templates (historically “ab initio” modeling). Progress was driven by the successful application of deep learning techniques to predict inter‐residue distances. In turn, these results drove dramatic improvements in three‐dimensional structure accuracy: With the proviso that there are an adequate number of sequences known for the protein family, the new methods essentially solve the long‐standing problem of predicting the fold topology of monomeric proteins. Further, the number of sequences required in the alignment has fallen substantially. There is also substantial improvement in the accuracy of template‐based models. Other areas—model refinement, accuracy estimation, and the structure of protein assemblies—have again yielded interesting results. CASP13 placed increased emphasis on the use of sparse data together with modeling and chemical crosslinking, SAXS, and NMR all yielded more mature results. This paper summarizes the key outcomes of CASP13. The special issue of PROTEINS contains papers describing the CASP13 assessments in each modeling category and contributions from the participants.

This article is an introduction to the special issue of the journal PROTEINS, dedicated to the tenth Critical Assessment of Structure Prediction (CASP) experiment to assess the state of the art in protein structure modeling. The article describes the conduct of the experiment, the categories of prediction included, and outlines the evaluation and assessment procedures. The 10 CASP experiments span almost 20 years of progress in the field of protein structure modeling, and there have been enormous advances in methods and model accuracy in that period. Notable in this round is the first sustained improvement of models with refinement methods, using molecular dynamics. For the first time, we tested the ability of modeling methods to make use of sparse experimental three-dimensional contact information, such as may be obtained from new experimental techniques, with encouraging results. On the other hand, new contact prediction methods, though holding considerable promise, have yet to make an impact in CASP testing. The nature of CASP targets has been changing in recent CASPs, reflecting shifts in experimental structural biology, with more irregular structures, more multi-domain and multi-subunit structures, and less standard versions of known folds. When allowance is made for these factors, we continue to see steady progress in the overall accuracy of models, particularly resulting from improvement of non-template regions.

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This article reports the outcome of the 12th round of Critical Assessment of Structure Prediction (CASP12), held in 2016. CASP is a community experiment to determine the state of the art in modeling protein structure from amino acid sequence. Participants are provided sequence information and in turn provide protein structure models and related information. Analysis of the submitted structures by independent assessors provides a comprehensive picture of the capabilities of current methods, and allows progress to be identified. This was again an exciting round of CASP, with significant advances in 4 areas: (i) The use of new methods for predicting three-dimensional contacts led to a two-fold improvement in contact accuracy. (ii) As a consequence, model accuracy for proteins where no template was available improved dramatically. (iii) Models based on a structural template showed overall improvement in accuracy. (iv) Methods for estimating the accuracy of a model continued to improve. CASP continued to develop new areas: (i) Assessing methods for building quaternary structure models, including an expansion of the collaboration between CASP and CAPRI. (ii) Modeling with the aid of experimental data was extended to include SAXS data, as well as again using chemical cross-linking information. (iii) A team of assessors evaluated the suitability of models for a range of applications, including mutation interpretation, analysis of ligand binding properties, and identification of interfaces. This article describes the experiment and summarizes the results. The rest of this special issue of PROTEINS contains papers describing CASP12 results and assessments in more detail.

Critical assessment of structure prediction (CASP) is a community experiment to advance methods of computing three-dimensional protein structure from amino acid sequence. Core components are rigorous blind testing of methods and evaluation of the results by independent assessors. In the most recent experiment (CASP14), deeplearning methods from one research group consistently delivered computed structures rivaling the corresponding experimental ones in accuracy. In this sense, the results represent a solution to the classical protein-folding problem, at least for single proteins. The models have already been shown to be capable of providing solutions for problematic crystal structures, and there are broad implications for the rest of structural biology. Other research groups also substantially improved performance.Here, we describe these results and outline some of the many implications. Other related areas of CASP, including modeling of protein complexes, structure refinement, estimation of model accuracy, and prediction of inter-residue contacts and distances, are also described.