title: Improved reliability, accuracy and quality in automated NMR structure calculation with ARIA.
abstract: In biological NMR, assignment of NOE cross-peaks and calculation of atomic conformations are critical steps in the determination of reliable high-resolution structures. ARIA is an automated approach that performs NOE assignment and structure calculation in a concomitant manner in an iterative procedure. The log-harmonic shape for distance restraint potential and the Bayesian weighting of distance restraints, recently introduced in ARIA, were shown to significantly improve the quality and the accuracy of determined structures. In this paper, we propose two modifications of the ARIA protocol: (1) the softening of the force field together with adapted hydrogen radii, which is meaningful in the context of the log-harmonic potential with Bayesian weighting, (2) a procedure that automatically adjusts the violation tolerance used in the selection of active restraints, based on the fitting of the structure to the input data sets. The new ARIA protocols were fine-tuned on a set of eight protein targets from the CASD-NMR initiative. As a result, the convergence problems previously observed for some targets was resolved and the obtained structures exhibited better quality. In addition, the new ARIA protocols were applied for the structure calculation of ten new CASD-NMR targets in a blind fashion, i.e. without knowing the actual solution. Even though optimisation of parameters and pre-filtering of unrefined NOE peak lists were necessary for half of the targets, ARIA consistently and reliably determined very precise and highly accurate structures for all cases. In the context of integrative structural biology, an increasing number of experimental methods are used that produce distance data for the determination of 3D structures of macromolecules, stressing the importance of methods that successfully make use of ambiguous and noisy distance data.
authors: Unité de Bioinformatique Structurale, CNRS UMR 3528, Institut Pasteur, 25-28 rue du Dr Roux, 75724, Paris Cedex 15, France.|Cellule d'Informatique pour la Biologie, Institut Pasteur, 25-28 rue du Dr Roux, 75724, Paris Cedex 15, France.
authors: Fabien
authors: F
authors: Mareuil
authors: Unité de Bioinformatique Structurale, CNRS UMR 3528, Institut Pasteur, 25-28 rue du Dr Roux, 75724, Paris Cedex 15, France.
authors: Thérèse E
authors: TE
authors: Malliavin
authors: Unité de Bioinformatique Structurale, CNRS UMR 3528, Institut Pasteur, 25-28 rue du Dr Roux, 75724, Paris Cedex 15, France.
authors: Michael
authors: M
authors: Nilges
authors: Unité de Bioinformatique Structurale, CNRS UMR 3528, Institut Pasteur, 25-28 rue du Dr Roux, 75724, Paris Cedex 15, France. bardiaux@pasteur.fr.
authors: Benjamin
authors: B
authors: Bardiaux
mesh_terms: D001331:Automation / Q000379:methods*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results
chemical_list: D011506:Proteins
keywords: ARIA; Automated NOE assignment; CASD–NMR; Nuclear magnetic resonance; Structure determination