title: CAD-score: a new contact area difference-based function for evaluation of protein structural models.
abstract: Evaluation of protein models against the native structure is essential for the development and benchmarking of protein structure prediction methods. Although a number of evaluation scores have been proposed to date, many aspects of model assessment still lack desired robustness. In this study we present CAD-score, a new evaluation function quantifying differences between physical contacts in a model and the reference structure. The new score uses the concept of residue-residue contact area difference (CAD) introduced by Abagyan and Totrov (J Mol Biol 1997; 268:678-685). Contact areas, the underlying basis of the score, are derived using the Voronoi tessellation of protein structure. The newly introduced CAD-score is a continuous function, confined within fixed limits, free of any arbitrary thresholds or parameters. The built-in logic for treatment of missing residues allows consistent ranking of models of any degree of completeness. We tested CAD-score on a large set of diverse models and compared it to GDT-TS, a widely accepted measure of model accuracy. Similarly to GDT-TS, CAD-score showed a robust performance on single-domain proteins, but displayed a stronger preference for physically more realistic models. Unlike GDT-TS, the new score revealed a balanced assessment of domain rearrangement, removing the necessity for different treatment of single-domain, multi-domain, and multi-subunit structures. Moreover, CAD-score makes it possible to assess the accuracy of inter-domain or inter-subunit interfaces directly. In addition, the approach offers an alternative to the superposition-based model clustering. The CAD-score implementation is available both as a web server and a standalone software package at http://www.ibt.lt/bioinformatics/cad-score/.
authors.affiliation: Institute of Biotechnology, Vilnius University, Graičiūno 8, LT-02241 Vilnius, Lithuania.
authors.forename: Kliment
authors.initials: K
authors.lastname: Olechnovič
authors.forename: Eleonora
authors.initials: E
authors.lastname: Kulberkytė
authors.forename: Ceslovas
authors.initials: C
authors.lastname: Venclovas
mesh_terms: D019295:Computational Biology / Q000379:methods*; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D020539:Sequence Analysis, Protein / Q000379:methods*; D018709:Statistics, Nonparametric
chemical_list: D011506:Proteins