2.2.1 | Domain-domain interactions
For CASP assessment, some protein structures are divided into multiple
evaluation units, splitting along domain boundaries, on the basis of
relatively low GDT_TS values for the whole structure compared to the
separate EUs (18). In this sense, apparently high accuracy may apply to
only part of a structure, giving a misleading impression. To investigate
this point and other aspects of domains, the protein assembly assessor
analyzed the accuracy of the relevant domain-domain interfaces using the
same methods as for subunit-subunit interfaces (11). In CASP15, 22 of
the 77 tertiary structure targets were split into two or more EUs
resulting in 112 evaluation units (18). Of these 22 structures, 15 have
insufficient interactions between the EUs to stabilize a fixed
relationship (using a threshold of less than 10 interface inter-residue
contacts, where a contact is any residue-residue interatomic distance of
less than 5Å). The remaining seven targets have 21 inter-EU interactions
in total. Domain-domain interface agreement with experiment is expressed
as the Interface Contact Score (ICS), equivalent to F1 for
residue-residue contacts across an interface (maximum value 1.0). Poor
ICS scores tend to occur in larger proteins. Of the 21 interfaces, only
two are in proteins of less than 1000 residues and these have relatively
high ICS values of 0.88 and 0.99. There is generally more flexibility
across domain interfaces than within domains, and ICS is sensitive to
small changes. Assuming ICS values greater than 0.8 approach
experimental uncertainty limits, all interfaces in shorter proteins and
seven of the 19 interfaces in larger proteins (>1000
residues) are accurate.