CASP9 assessment of free modeling target predictions

Abstract

We present an overview of the ninth round of Critical Assessment of Protein Structure Prediction (CASP9) ‘Template free modeling’ category (FM). Prediction models were evaluated using a combination of established structural and sequence comparison measures and a novel automated method designed to mimic manual inspection by capturing both global and local structural features. These scores were compared to those assigned manually over a diverse subset of target domains. Scores were combined to compare overall performance of participating groups and to estimate rank significance. Moreover, we discuss a few examples of free modeling targets to highlight the progress and bottlenecks of current prediction methods. Notably, a server prediction model for a single target (T0581) improved significantly over the closest structure template (44% GDT increase). This accomplishment represents the ‘winner’ of the CASP9 FM category. A number of human expert groups submitted slight variations of this model, highlighting a trend for human experts to act as “meta predictors” by correctly selecting among models produced by the top-performing automated servers. The details of evaluation are available at http://prodata.swmed.edu/CASP9/

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.…”

Bioinformatics and variability in drug response: a protein structural perspective

“…Recent CASP results indicate free modelling method performance is highly dependent on target length, with an apparent upper limit of 120 residues [214]. Similarly, accurate prediction of multi-domain structures remains a significant challenge [215]. Much room for improvement remains; evaluation of 16 971 free modelling predictions of 30 target sequences in CASP9 showed that even top-performing technologies produced a number of physically unrealistic models [215].…”

Reduced Fragment Diversity for Alpha and Alpha-Beta Protein Structure Prediction using Rosetta

“…Regardless of the fragments' length used by those methods, their popularity is supported by three main points: (1) since the "smallest element" considered in computation is a set of amino acids instead of a single one, entropy in conformational search space is decreased in a dramatic way, (2) short sub-sequences converge towards a relatively limited number of sub-structures and (3) usage of Monte Carlo simulations instead of Molecular Dynamics ones has allowed making those methods much faster than pure ab initio ones. Nevertheless, fragmentbased methods continue to fail reaching reasonable accuracy for many CASP's targets, which has motivated further improvements, amendments and tuning [16] [30]. This may be explained by the fact that, unlike FRAGFOLD, I-TASSER and QUARK which use relatively long fragments, Rosetta conforms to the original study of fragment assembly PSP conducted by Bowie and Eisenberg by taking into consideration short fragments [31].…”