Scoring predictive models using a reduced representation of proteins: model and energy definition

Abstract

Background: Reduced representations of proteins have been playing a keyrole in the study of protein folding. Many such models are available, with different representation detail. Although the usefulness of many such models for structural bioinformatics applications has been demonstrated in recent years, there are few intermediate resolution models endowed with an energy model capable, for instance, of detecting native or native-like structures among decoy sets. The aim of the present work is to provide a discrete empirical potential for a reduced protein model termed here PC2CA, because it employs a PseudoCovalent structure with only 2 Centers of interactions per Amino acid, suitable for protein model quality assessment.

Results: All protein structures in the set top500H have been converted in reduced form. The distribution of pseudobonds, pseudoangle, pseudodihedrals and distances between centers of interactions have been converted into potentials of mean force. A suitable reference distribution has been defined for non-bonded interactions which takes into account excluded volume effects and protein finite size. The correlation between adjacent main chain pseudodihedrals has been converted in an additional energetic term which is able to account for cooperative effects in secondary structure elements. Local energy surface exploration is performed in order to increase the robustness of the energy function.

Conclusion: The model and the energy definition proposed have been tested on all the multiple decoys' sets in the Decoys'R'us database. The energetic model is able to recognize, for almost all sets, native-like structures (RMSD less than 2.0 A). These results and those obtained in the blind CASP7 quality assessment experiment suggest that the model compares well with scoring potentials with finer granularity and could be useful for fast exploration of conformational space. Parameters are available at the url: http://www.dstb.uniud.it/~ffogolari/download/.

Figure 1

Energy versus RMSD plots for the 4state decoy sets.

Figure 2

GDT_TS of the best PC2CA scoring models (black triangles)and average GDT_TS of predictive models (red circles) versus GDT_TS of the best predictive model for each target in CASP7 MQAP.

Figure 3

Pseudocovalent structure for a five-residue fragment of a protein (PDB id 1CTF, fragment 54–58).

Figure 4

Original histogram of counts for the distances between the Ile and Ala sidechain centers of interaction (bin width = 0.25 Å) (upper panel). Computed radial distribution function (lower panel).