Assessment of template based protein structure predictions in CASP9

Abstract

In the Ninth Edition of the Critical Assessment of Techniques for Protein Structure Prediction (CASP9), 61,665 models submitted by 176 groups were assessed for their accuracy in the template based modeling category. The models were evaluated numerically in comparison to their experimental control structures using two global measures (GDT and GDC), and a novel local score evaluating the correct modeling of local interactions (lDDT). Overall, the state of the art of template based modeling in CASP9 is high, with many groups performing well. Among the methods registered as prediction "servers", six independent groups are performing on average better than the rest. The submissions by "human" groups are dominated by meta-predictors, with one group performing noticeably better than the others. Most of the participating groups failed to assign realistic confidence estimates to their predictions, and only a very small fraction of the assessed methods have provided highly accurate models and realistic error estimates at the same time. Also, the accuracy of predictions for homo-oligomeric assemblies was overall poor, and only one group performed better than a naïve control predictor. Here, we present the results of our assessment of the CASP9 predictions in the category of template based modeling, documenting the state of the art and highlighting areas for future developments.

Biophysics of protein evolution and evolutionary protein biophysics

“…This enriched methodology provides more accurate evolutionary inference than approaches that do not consider the conformational context of the mutation sites, but it requires the 3D structure of the protein in question. Hopefully, with better protein structure prediction techniques [437,438], it may be possible to apply structure-based phylogenetic reconstruction methods routinely by starting with sequence information alone.…”

β‐Bulges: Extensive structural analyses of β‐sheets irregularities

“…This latter varying between 0 and 100, and reflects the global similarity of two protein structures. It was used for model assessment in the last rounds of critical assessment of techniques for protein structure prediction 60 .…”

Compare local pocket and global protein structure models by small structure patterns

“…For each pair of predicted and native models conducted from CASP10, the GDT-TS scores [32] are calculated using our method and state-of-the-art LGA method [31]. Previously, the GDT-TS score and the LGA method have been used by CASP competitions since 1998 [32,16,10,12]. In this study, the GDT-TS scores are normalized by the number of corresponding residue pairs between predicted and native models, and N is set to be the smallest meaningful value of 3.…”

“…As LGA [31] has been the reference method to calculate GDT-TS scores [32] in previous CASP competitions [32,16,10,12], we compared the GDT-TS scores calculated by our method and those calculated by LGA in Figure 2(f). Since the final refinement step based on large subsets are not applied in this experiment, only small subsets of size 6 have been used in our method here.…”