A global analysis of NMR distance constraints from the PDB

Abstract

Information obtained from Nuclear Magnetic Resonance (NMR) experiments is encoded as a set of constraint lists when calculating three-dimensional structures for a protein. With the amount of constraint data from the world wide Protein Data Bank (wwPDB) that is now available, it is possible to do a global, large-scale analysis using only information from the constraints, without taking the coordinate information into account. This article describes such an analysis of distance constraints from NOE data based on a set of 1834 NMR PDB entries containing 1909 protein chains. In order to best represent the quality and extent of the data that is currently deposited at the wwPDB, only the original data as deposited by the authors was used, and no attempt was made to 'clean up' and further interpret this information. Because the constraint lists provide a single set of data, and not an ensemble of structural solutions, they are easier to analyse and provide a reduced form of structural information that is relevant for NMR analysis only. The online resource resulting from this analysis ( http://www.ebi.ac.uk/msd/srv/docs/NMR/analysis/results/html/comparison.html ) makes it possible to check, for example, how often a particular contact occurs when assigning NOESY spectra, or to find out whether a particular sequence fragment is likely to be difficult to assign. In this respect it formalises information that scientists with experience in spectrum analysis are aware of but cannot necessarily quantify. The analysis described here illustrates the importance of depositing constraints (and all other possible NMR derived information) along with the structure coordinates, as this type of information can greatly assist the NMR community.

Fig. 1

Overview of the workflow employed in the analysis. Grey boxes indicate files, white boxes Python scripts

Fig. 2

Example web page for Ala → Ala i → i + 2 contact information from http://www.ebi.ac.uk/msd-srv/docs/NMR/analysis/results/html/comparison.html. The different data sets, comparisons between them, and analysis categories can be accessed via the left hand side menu. In this contact information page, overall statistics for the individual Ala residues involved in this contact are shown in the ‘Residue 1’ and ‘Residue 2’ tables at the top, statistics for the combined Ala–Ala residues in the ‘Residue combination’ table. The information on an atom level is listed in the ‘Breakdown per contact’ table. Outliers per secondary structure combination based on a binomial analysis are highlighted in red (higher than expected) and blue (lower than expected). This colour coding is used throughout the web pages for other types of analyses

Fig. 3

Correlation between the f_occurrence for the HP and AHIP data sets (correlation Spearman 0.971, Pearson 0.996)

Fig. 4

Distance distribution from the constraint information for sequential Ala–Ala contacts between backbone H protons

Fig. 5

Correlation between the f_occurrence from the HPC (Coordinates) and HP (Constraint) sets