Protein structural variation in computational models and crystallographic data - PubMed (original) (raw)

Protein structural variation in computational models and crystallographic data

Dmitry A Kondrashov et al. Structure. 2007 Feb.

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Abstract

Normal mode analysis offers an efficient way of modeling the conformational flexibility of protein structures. We use anisotropic displacement parameters from crystallography to test the quality of prediction of both the magnitude and directionality of conformational flexibility. Normal modes from four simple elastic network model potentials and from the CHARMM force field are calculated for a data set of 83 diverse, ultrahigh-resolution crystal structures. While all five potentials provide good predictions of the magnitude of flexibility, all-atom potentials have a clear edge at prediction of directionality, and the CHARMM potential has the highest prediction quality. The low-frequency modes from different potentials are similar, but those computed from the CHARMM potential show the greatest difference from the elastic network models. The comprehensive evaluation demonstrates the costs and benefits of using normal mode potentials of varying complexity.

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Figures

Figure 1

Figure 1

Example of a high-resolution protein structure (PDB ID 1R6J) showing anisotropic temperature factors for backbone atoms. The ellipsoids represent 90% probability volume of atomic position, with color varying from immobile (blue) to more mobile (red). Most of the backbone atoms are not mobile and isotropic, with a few loop residues (residue numbers labeled) showing clear directional preference in positional distribution.

Figure 2

Figure 2

Distributions of anisotropy parameters in structures refined with SHELX and Refmac software. The large difference is likely due to different default restraints on the anisotropic parameters in the two.

Figure 3

Figure 3

Overlap scores for individual normal modes from different potentials averaged over all 83 structures. Each curve is a comparison between a pair of potentials for the 17 lowest frequency modes. The solid curves compare different ENM-like potentials, while the dotted curves compare CHARMM-based BNM results with those from ENM potentials.

Figure 4

Figure 4

Correlation matrices generated from normal mode analyses of PDZ domain (PDB ID 1R6J). The plots show correlation between residues with indices shown on x and y axes, blue color indicating negative correlation and red signifying positive, with the range shown in the colorbars. Secondary structure elements are labeled in sequence order. A) Correlation from Anisotropic Network Model; B) from CHARMM-based Block Normal Modes. Note that the range in plot A is half that of B.

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