Compliance of NMR-derived Structural Ensembles with experimental data
+ selection

The CoNSEnsX web server - description

Ensemble evaluation

The server is designed to analyze structural ensembles generated to represent the internal dynamics of proteins (see e.g. Ángyán & Gáspári 2013 and references therein). Such ensembles are expected to reflect NMR-derived experimental parameters in an ensemble-averaged manner, i.e. the ensemble as a whole corresponds to the parameters better than any of its constituent conformers, whereas the diversity of the conformations is related to the internal motions observed at a given time scale. For example, S2 general order parameters derived from heteronuclear relaxation measurements can be used to restrain MD simulations to generate ensembles reflecting internal dynamics at the ps-ns time scale (Best & Vendruscolo 2004, Lindorff-Larsen et al. 2005, Richter et al. 2007). The aim of the CoNSEnsX approach is to provide a convenient and standardized way to evaluate such ensembles. The server reports the correspondence of the ensemble to each NMR parameter separately and does not yield a single quality measure. The justification for this that the availability and reliability of different types of parameters varies from case to case, and the relevance and usability of an ensemble should be decided based on this information as well as the purpose of its generation (i.e. what biological phenomenon was intended to be addressed with it).
The server is designed to analyze as many types of parameters as possible from those supplied with the BMRB-format NMR parameter file (parsing is performed using a Python3 port of the NMRPyStar package). Currently the server supports the following parameters:

The server reports the correlation and RMSD for each parameter as well as Q-factor for RDCs. In addition, a correlation plot, a per-residue correspondence plot and a plot comparing the correlation of the ensemble as a whole vs. the individual conformers and the average of per-conformer correlations.

Sub-ensemble selection

The CoNSEnsX server is capable of selecting a sub-ensemble with the best match to selected experimental data. Selection can be initiated after a round of evaluation by specifying the parameters to be included in the selection process along with their weights (on a scale of 0 to 10). This kind of selection is admittedly subjective but allows the user to discriminate between parameters on the basis of their reliability and importance for the actual task.
The selection algorithm currently implemented is a version of a greedy approach, starting from the single conformer best corresponding to the included parameters and gradually adding conformers requiring better correspondence whenever possible. A so-called overdrive parameter can be set to allow individual addition steps to yield worse correspondence than the previous ones - extending the ensemble by further members might yield an overall better correspondence even in such cases. The other main adjustable parameters are the minimum and maximum size of the final sub-ensemble to be returned as well as the measure by which the sub-ensembles will be evaluated (Pearson correlation, Q-factor or RMSD). The output is the correspondence of the parameters to the full ensmeble and the selected sub-ensemble as well as the sub-ensemble as a downloadable PDB file.

Test data set

The test data set provided for the server is based on an ensemble calculated for the N-terminal SH3 domain of the DRK protein (PDB entry 2A36, Bezsonova et. al 2005) using standard molecular dynamics simulations. The test ensemble is a subsection of the ‘reference ensemble’ described in the CoNSEnsX+ paper (specifically, it contains 12 in addition to the ‘constricted ensemble’ to allow testing of the selection feature). The NMR parameter set provided contains backbone S2 order parameters, chemical shifts and with five RDC sets calculated from the ensemble. More details can be found in the CoNSEnsX+ paper.


The server currently supports ensembles up to 1000 conformers.

Versions & availability

The current CoNSEnsX version is a complete redesign of the original one. The source code is free and available at GitHub
. The first version of the server is still available at and was described in: Ángyán et al. BMC Strut. Biol. 2010, 10:39.

Tools & tips

Several scripts for conversion between different formats are provided here in the hope that they might be useful. They are simple scripts and might not cover all issues arising during format conversion. They can be freely used and modified but come with absolutely no warranty. The 'disre' format is introduced as a format highly similar to the distabce restraint format in GROMACS topology files, with all atoms explicitly named and atom pairs corresponding to the same restraint forming a group.
We recommend that before uploading data to the CoNSEnsX server, the user goes through the following steps: