Structure similarity measure with penalty for close non-equivalent residues

Motivation: Recent improvement in homology-based structure modeling emphasizes the importance of sensitive evaluation measures that help identify and correct modest distortions in models compared with the target structures. Global Distance Test Total Score (GDT_TS), otherwise a very powerful and effective measure for model evaluation, is still insensitive to and can even reward such distortions, as observed for remote homology modeling in the latest CASP8 (Comparative Assessment of Structure Prediction). Results: We develop a new measure that balances GDT_TS reward for the closeness of equivalent model and target residues (`attraction' term) with the penalty for the closeness of non-equivalent residues ('repulsion' term). Compared with GDT_TS, the resulting score, TR (total score with repulsion), is much more sensitive to structure compression both in real remote homologs and in CASP models. TR is correlated yet different from other measures of structure similarity. The largest difference from GDT_TS is observed in models of mid-range quality based on remote homology modeling.