Assessment of chemical‐crosslink‐assisted protein structure modeling in CASP13

Abstract

With the advance of experimental procedures obtaining chemical crosslinking information is becoming a fast and routine practice. Information on crosslinks can greatly enhance the accuracy of protein structure modeling. Here, we review the current state of the art in modeling protein structures with the assistance of experimentally determined chemical crosslinks within the framework of the 13th meeting of Critical Assessment of Structure Prediction approaches. This largest‐to‐date blind assessment reveals benefits of using data assistance in difficult to model protein structure prediction cases. However, in a broader context, it also suggests that with the unprecedented advance in accuracy to predict contacts in recent years, experimental crosslinks will be useful only if their specificity and accuracy further improved and they are better integrated into computational workflows.

Critical assessment of methods of protein structure prediction (CASP)—Round XIII

“…Based on these data, five heteromeric targets and 17 single‐sequence targets (monomers or subunits of multimers) were released for prediction. An analysis by the assessor shows that a surprisingly high fraction of cross‐links appear not to be compatible with the targets' X‐ray structures (27%‐47%). In total, 14 prediction groups participated.…”

“…Many cross‐links are misleading in that they conflict with the corresponding X‐ray structure and some can be false positives. Further, the large variation in distance between crosslinked residues makes the technique inherently low‐resolution, and so likely best suited to complexes, as the result for X0957 illustrates.…”

Assessment of protein assembly prediction in CASP13

“…Thus, we looked into contact predictions in relation to quaternary structure modeling. Although interface contacts are not considered in the contact prediction category in CASP13, 35 homomeric interfaces are formed by contacts within a single target and should therefore be accounted for. In total, 37 CASP13 targets form homomeric interactions, which in average account for 13% of all contacts in the target, ranging from 2% to over Figure S1).…”

“…The experimental details and data-assisted specific assessment is discussed in the respective articles. 35,42 Here, as part of our assembly analysis, we looked into how the data-assisted assembly predictions compare with the regular ones, using the regular evaluation strategy. All seven targets were selected from the difficult group, for which there is little homology information available to perform traditional modeling.…”

“…The other subunit attaches on either side of the beta sheets experimental data and structural data (crystallography), which is discussed in the accompanying articles in this issue. 35,42…”