Systematic comparison of crystal and NMR protein structures deposited in the protein data bank

Abstract

Nearly all the macromolecular three-dimensional structures deposited in Protein Data Bank were determined by either crystallographic (X-ray) or Nuclear Magnetic Resonance (NMR) spectroscopic methods. This paper reports a systematic comparison of the crystallographic and NMR results deposited in the files of the Protein Data Bank, in order to find out to which extent these information can be aggregated in bioinformatics. A non-redundant data set containing 109 NMR - X-ray structure pairs of nearly identical proteins was derived from the Protein Data Bank. A series of comparisons were performed by focusing the attention towards both global features and local details. It was observed that: (1) the RMDS values between NMR and crystal structures range from about 1.5 Å to about 2.5 Å; (2) the correlation between conformational deviations and residue type reveals that hydrophobic amino acids are more similar in crystal and NMR structures than hydrophilic amino acids; (3) the correlation between solvent accessibility of the residues and their conformational variability in solid state and in solution is relatively modest (correlation coefficient = 0.462); (4) beta strands on average match better between NMR and crystal structures than helices and loops; (5) conformational differences between loops are independent of crystal packing interactions in the solid state; (6) very seldom, side chains buried in the protein interior are observed to adopt different orientations in the solid state and in solution.

Keywords: Large scale structure comparison; NMR spectroscopy; Protein Data Bank; X-ray crystallography.; structure similarity.

Fig. (1)

Distribution of the RMDS (top) and RMDS₁₀₀ values (bottom) calculated between the equivalent X-ray and NMR protein models superposed (Cα atoms only) by either CE or DALI or PROFIT. In the case where the PDB entry corresponding to a NMR structure contains several models, all of them were considered separately.

Fig. (2)

(a) Distribution of side chain RMSD after optimal superposition of all Cα atoms (only for the cases in which the RMSD of the Cα atoms is lower than 1 Å). When the PDB entry corresponding to a NMR structure contains several models, values were averaged. The values reported in the figure are thus averages of averages. (b) Mean side chain RMSD shown on per residue type basis. RMSD is calculated on a basis of all side chain atoms excluding hydrogen atoms.

Fig. (3)

Correlation between the residue solvent accessibility and the RMDS for the corresponding side chains (after their optimal superposition). The linear trend line is shown (straight line) together with the confidence interval at the 0.99 probability level (curved lines).

Fig. (4)

Correlation between equivalent Cα atom distances (after their optimal superposition) and RMSD for the corresponding side chains. The linear trend line is shown (straight line) together with the confidence interval at the 0.99 probability level (curved lines).

Fig. (5)

Example of differently oriented side chain in a case where two Cα atoms are well superposed. Most of these cases refer to residues that are very exposed to the solvent. Only very few cases refer to residues that are buried in the protein interior. This is the case of Tyr 48 in (a) 1W8L (X-ray structure) and (b) model 1 of 1OCA (NMR structure). Figure is prepared using PyMOL [64].