AlphaKnot 2.0: a web server for the visualization of proteins' knotting and a database of knotted AlphaFold-predicted models

Abstract

The availability of 3D protein models is rapidly increasing with the development of structure prediction algorithms. With the expanding availability of data, new ways of analysis, especially topological analysis, of those predictions are becoming necessary. Here, we present the updated version of the AlphaKnot service that provides a straightforward way of analyzing structure topology. It was designed specifically to determine knot types of the predicted structure models, however, it can be used for all structures, including the ones solved experimentally. AlphaKnot 2.0 provides the user's ability to obtain the knowledge necessary to assess the topological correctness of the model. Both probabilistic and deterministic knot detection methods are available, together with various visualizations (including a trajectory of simplification steps to highlight the topological complexities). Moreover, the web server provides a list of proteins similar to the queried model within AlphaKnot's database and returns their knot types for direct comparison. We pre-calculated the topology of high-quality models from the AlphaFold Database (4th version) and there are now more than 680.000 knotted models available in the AlphaKnot database. AlphaKnot 2.0 is available at https://alphaknot.cent.uw.edu.pl/.

Graphical Abstract

Figure 1.

Web Server features. (A) Submission options—default and additional parameters. The user can choose from several options of how the topology will be calculated in the structure (including the accuracy). New features provided with the updated AlphaKnot 2.0 are marked with blue and the AlphaKnot’s logo. Please note, that the calculation time is directly related to the selected parameters but also the length and complexity of the structure. For a single structure, it varies from a few seconds to several hours. (B) Frames showing simplification of the structure using knot_pull algorithm (based on UniProtKB ID: F1QYU7).

Figure 2.

Database protein page—default and additional features. Additional features available after recomputing the model in the Web Server are marked with dashed lines. New features provided with the updated AlphaKnot are marked with the AlphaKnot’s 2.0 logo. (A) UniProtKB ID of the protein, model number, and protein name. (B) Available tabs. (C) Categories voted by users. (D) Button for submitting the current model to our Web Server. (E) Basic information about the protein and the model. (F) knot map with the slider applying different knot probability cutoffs. (G) 3D structure of the model. (H) Trajectory of simplification steps. (I) Information about found knots. (J) Comment section.