NMR Constraints Analyser: a web-server for the graphical analysis of NMR experimental constraints

Abstract

Nuclear magnetic resonance (NMR) spectroscopy together with X-ray crystallography, are the main techniques used for the determination of high-resolution 3D structures of biological molecules. The output of an NMR experiment includes a set of lower and upper limits for the distances (constraints) between pairs of atoms. If the number of constraints is high enough, there will be a finite number of possible conformations (models) of the macromolecule satisfying the data. Thus, the more constraints are measured, the better defined these structures will be. The availability of a user-friendly tool able to help in the analysis and interpretation of the number of experimental constraints per residue, is thus of valuable importance when assessing the levels of structure definition of NMR solved biological macromolecules, in particular, when high-quality structures are needed in techniques such as, computational biology approaches, site-directed mutagenesis experiments and/or drug design. Here, we present a free publicly available web-server, i.e. NMR Constraints Analyser, which is aimed at providing an automatic graphical analysis of the NMR experimental constraints atom by atom. The NMR Constraints Analyser server is available from the web-page http://molsim.sci.univr.it/constraint

Structure of the terminal PCP domain of the non‐ribosomal peptide synthetase in teicoplanin biosynthesis

“…Average structures for structural alignments were calculated with SuperPose 1.0 . NOE distributions per residue were analyzed with the NMR Constraint Analyzer and the calculated structures were compared to the restraints of the non‐corresponding state with CoNSENsX (Supporting Information Fig. S1).…”

CING: an integrated residue-based structure validation program suite

“…A more detailed quality analysis is typically performed using external programs such as PROCHECK_NMR/AQUA (Laskowski et al 1996 ), Molprobity (Lovell et al 2003 ), WHAT_CHECK (Hooft et al 1996b ), and sometimes Model Quality Assessment Programs (MQAPs) (McGuffin 2007 ). More recently, a visual validation web server, called NMR Constraints Analyser, has been presented (Heller and Giorgetti 2010 ) that focuses on the validation of the distance restraints. Other programs such as PSVS (Bhattacharya et al 2007 ), GLM (Bagaria et al 2012 ) and ResProx ( http://www.resprox.ca ) have combined several of the common tools with their own specific checks.…”

Contribution of high-energy conformations to NMR chemical shifts, a DFT-BOMD study

“…Indeed, most biosystems exist as conformers in dynamic equilibria, and their functional properties cannot be described using only a static structure as determined by X-ray crystallography or even by a set of structures obtained from experimental NMR constraints (taking into account the lower and upper limits of interatomic distances evaluated through experiment). 11 Conformational fluctuations of proteins involving multiple conformers of different energies are now studied using NMR spectroscopy at various pressures. 12,13 This new methodology provides different time-averaged NMR signals with different pressures for structural changes within about 1 ms to 1 s, allowing a realistic description of lowfrequency protein motions.…”