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Residue-level global and local ensemble-ensemble comparisons of protein domains.

ABSTRACT: Many methods of protein structure generation such as NMR-based solution structure determination and template-based modeling do not produce a single model, but an ensemble of models consistent with the available information. Current strategies for comparing ensembles lose information because they use only a single representative structure. Here, we describe the ENSEMBLATOR and its novel strategy to directly compare two ensembles containing the same atoms to identify significant global and local backbone differences between them on per-atom and per-residue levels, respectively. The ENSEMBLATOR has four components: eePREP (ee for ensemble-ensemble), which selects atoms common to all models; eeCORE, which identifies atoms belonging to a cutoff-distance dependent common core; eeGLOBAL, which globally superimposes all models using the defined core atoms and calculates for each atom the two intraensemble variations, the interensemble variation, and the closest approach of members of the two ensembles; and eeLOCAL, which performs a local overlay of each dipeptide and, using a novel measure of local backbone similarity, reports the same four variations as eeGLOBAL. The combination of eeGLOBAL and eeLOCAL analyses identifies the most significant differences between ensembles. We illustrate the ENSEMBLATOR's capabilities by showing how using it to analyze NMR ensembles and to compare NMR ensembles with crystal structures provides novel insights compared to published studies. One of these studies leads us to suggest that a "consistency check" of NMR-derived ensembles may be a useful analysis step for NMR-based structure determinations in general. The ENSEMBLATOR 1.0 is available as a first generation tool to carry out ensemble-ensemble comparisons.

SUBMITTER: Clark SA

PROVIDER: S-EPMC4570546 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Residue-level global and local ensemble-ensemble comparisons of protein domains.

Clark Sarah A SA Tronrud Dale E DE Karplus P Andrew PA

Protein science : a publication of the Protein Society 20150622 9

Many methods of protein structure generation such as NMR-based solution structure determination and template-based modeling do not produce a single model, but an ensemble of models consistent with the available information. Current strategies for comparing ensembles lose information because they use only a single representative structure. Here, we describe the ENSEMBLATOR and its novel strategy to directly compare two ensembles containing the same atoms to identify significant global and local b ...[more]

PMID: 26032515

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Project description:The atomic-level structural properties of proteins, such as bond lengths, bond angles, and torsion angles, have been well studied and understood based on either chemistry knowledge or statistical analysis. Similar properties on the residue-level, such as the distances between two residues and the angles formed by short sequences of residues, can be equally important for structural analysis and modeling, but these have not been examined and documented on a similar scale. While these properties are difficult to measure experimentally, they can be statistically estimated in meaningful ways based on their distributions in known proteins structures. Residue-level structural properties including various types of residue distances and angles are estimated statistically. A software package is built to provide direct access to the statistical data for the properties including some important correlations not previously investigated. The distributions of residue distances and angles may vary with varying sequences, but in most cases, are concentrated in some high probability ranges, corresponding to their frequent occurrences in either ?-helices or ?-sheets. Strong correlations among neighboring residue angles, similar to those between neighboring torsion angles at the atomic-level, are revealed based on their statistical measures. Residue-level statistical potentials can be defined using the statistical distributions and correlations of the residue distances and angles. Ramachandran-like plots for strongly correlated residue angles are plotted and analyzed. Their applications to structural evaluation and refinement are demonstrated. With the increase in both number and quality of known protein structures, many structural properties can be derived from sets of protein structures by statistical analysis and data mining, and these can even be used as a supplement to the experimental data for structure determinations. Indeed, the statistical measures on various types of residue distances and angles provide more systematic and quantitative assessments on these properties, which can otherwise be estimated only individually and qualitatively. Their distributions and correlations in known protein structures show their importance for providing insights into how proteins may fold naturally to various residue-level structures.

Dataset Information

Residue-level global and local ensemble-ensemble comparisons of protein domains.

Publications

Residue-level global and local ensemble-ensemble comparisons of protein domains.

Similar Datasets

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