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.