The structure assessment web server: for proteins, complexes and more.

The 'structure assessment' web server is a one-stop shop for interactive evaluation and benchmarking of structural models of macromolecular complexes including proteins and nucleic acids. A user-friendly web dashboard links sequence with structure information and results from a variety of state-of-the-art tools, which facilitates the visual exploration and evaluation of structure models. The dashboard integrates stereochemistry information, secondary structure information, global and local model quality assessment of the tertiary structure of comparative protein models, as well as prediction of membrane location. In addition, a benchmarking mode is available where a model can be compared to a reference structure, providing easy access to scores that have been used in recent CASP experiments and CAMEO. The structure assessment web server is available at https://swissmodel.expasy.org/assess.

Assessment of protein-ligand complexes in CASP15.

CASP15 introduced a new category, ligand prediction, where participants were provided with a protein or nucleic acid sequence, SMILES line notation, and stoichiometry for ligands and tasked with generating computational models for the three-dimensional structure of the corresponding protein-ligand complex. These models were subsequently compared with experimental structures determined by x-ray crystallography or cryoEM. To assess these predictions, two novel scores were developed. The Binding-Site Superposed, Symmetry-Corrected Pose Root Mean Square Deviation (BiSyRMSD) evaluated the absolute deviations of the models from the experimental structures. At the same time, the Local Distance Difference Test for Protein-Ligand Interactions (lDDT-PLI) assessed the ability of models to reproduce the protein-ligand interactions in the experimental structures. The ligands evaluated in this challenge range from single-atom ions to large flexible organic molecules. More than 1800 submissions were evaluated for their ability to predict 23 different protein-ligand complexes. Overall, the best models could faithfully reproduce the geometries of more than half of the prediction targets. The ligands' size and flexibility were the primary factors influencing the predictions' quality. Small ions and organic molecules with limited flexibility were predicted with high fidelity, while reproducing the binding poses of larger, flexible ligands proved more challenging.

Assessment of the assessment-All about complexes.

Predicting model quality is a fundamental component of any modeling procedure, and blind assessment of these methods constitutes a crucial aspect of the Critical Assessment of Protein Structure Prediction (CASP) experiment. Historically, the main focus was on assessing methods that predict global and per-residue accuracies in tertiary structure models. This focus shifted with the community's increased efforts in modeling complexes and assemblies. We asked the community to process the models from the CASP15 assembly category and provide estimates of the accuracy of the predicted quaternary structure, both globally and at the local interface level. Besides identifying remarkable accuracy of modeling groups in assessing their own predictions, we set up a benchmarking pipeline to highlight different aspects of quaternary structure models and introduced a simple consensus EMA method as baseline. While participating methods showed commendable performance, the baseline was difficult to surpass. It is important to point out that prediction performance varies for the individual CASP targets, highlighting potential areas of improvement and challenges ahead.

Continuous Automated Model EvaluatiOn (CAMEO) complementing the critical assessment of structure prediction in CASP12.

Every second year, the community experiment "Critical Assessment of Techniques for Structure Prediction" (CASP) is conducting an independent blind assessment of structure prediction methods, providing a framework for comparing the performance of different approaches and discussing the latest developments in the field. Yet, developers of automated computational modeling methods clearly benefit from more frequent evaluations based on larger sets of data. The "Continuous Automated Model EvaluatiOn (CAMEO)" platform complements the CASP experiment by conducting fully automated blind prediction assessments based on the weekly pre-release of sequences of those structures, which are going to be published in the next release of the PDB Protein Data Bank. CAMEO publishes weekly benchmarking results based on models collected during a 4-day prediction window, on average assessing ca. 100 targets during a time frame of 5 weeks. CAMEO benchmarking data is generated consistently for all participating methods at the same point in time, enabling developers to benchmark and cross-validate their method's performance, and directly refer to the benchmarking results in publications. In order to facilitate server development and promote shorter release cycles, CAMEO sends weekly email with submission statistics and low performance warnings. Many participants of CASP have successfully employed CAMEO when preparing their methods for upcoming community experiments. CAMEO offers a variety of scores to allow benchmarking diverse aspects of structure prediction methods. By introducing new scoring schemes, CAMEO facilitates new development in areas of active research, for example, modeling quaternary structure, complexes, or ligand binding sites.