Figure 1. PyMOL22 target renderings
(left) and Grishin plots (right) for two two-domain targets:(A) target T1112, a protein involved in the synthesis of an
osmolyte involved in thermoadaptation, and (B) target T1124, a
methyltransferase MfnG (PDB: 7UX8). Grishin plots are built on the
GDT_TS scores for all collected models. The plots suggest evaluating
domains together as the angle between the data trend line and the
diagonal is small (i.e., the evaluation scores for the combined domains
(X-axis) and individual domains (Y-axis) are similar for most groups).
The last target in this category, T1180, is an exception to the
splitting rule (section 2.1 ). Even though the Grishin plot
advised splitting, we did not proceed with that as the target is a
fusion enzyme of two known domains, where the only prediction interest
was to model inter-domain orientation.
3.1.3 | Multidomain-targets requiring splitting (20)
For half of the 20 targets that required splitting, the number of EUs
was determined by the number of structural domains (no merging was
necessary), and for the other half, some domains but not all were
joined.
In several cases splitting was required because different chains
exhibited different folding patterns.
For example, target T1120, a DNA-binding protein DdrC, is composed of an
N-terminal winged helix-turn-helix motif and a C-terminal four-helix
bundle, that folds as an asymmetric domain-swapped dimer (Figure 2A)23. Superposition of
the two chains revealed the distortion of the long central helix hA in
chain A (cyan) into two smaller, non-colinear helices
(hB1 and hB2) in chain B (green) and
cause a shift in the relative position of the C-terminal domain with
regards to the anchor N-terminal domain (Figure 2B). This prompted
splitting of the target into two EUs at the break point (residue 125).
Such a split is strongly supported by the Grishin plot (Figure 2C).