Step 4: joining domains into larger evaluation units based on the performance.
Once domains were defined, models were trimmed accordingly and evaluated against the domains and their pair-wise combinations. GDT_TS scores from LGA’s sequence-dependent superpositions served as the numerical basis for deciding whether domains should be kept separate or combined into larger Evaluation Units (EUs) for the final evaluation.
A rationale and numeric procedure for combining domains /splitting targets into evaluation units were suggested by Nick Grishin and coworkers in CASP9 6. They argued that targets should be split into domains only if this can help reveal interesting predicted features in models. Rephrasing this postulate for the bottom-to-top approach (split first, then consider re-joining), domains should be merged if their separate evaluation does not provide additional benefits for the assessment. A good indicator of this scenario is the similarity of model accuracy scores on the combined and individual domains. To facilitate the decision-making, Kinch et al6 plotted GDT_TS scores for combined domains versus the weighted sum of scores for individual domains. Such a graph became later known as the Grishin plot and was adopted for defining EUs in subsequent CASPs6-10,20. If the points in such a graph line up close to the diagonal line, then joining a pair of domains into a larger evaluation unit is advised.
In CASP15, domains were joined if the slope of the zero-intercept best fit line in a Grishin plot was <1.2. Three or more domains were joined into one EU when the plots for all pairwise domain combinations supported the merger.
The process was repeated iteratively until no further combining of EUs was needed.