A robust method for determining the magnitude of the fully asymmetric alignment tensor of oriented macromolecules in the absence of structural information.

  title={A robust method for determining the magnitude of the fully asymmetric alignment tensor of oriented macromolecules in the absence of structural information.},
  author={G. Marius Clore and Angela M. Gronenborn and Adriaan Bax},
  journal={Journal of magnetic resonance},
  volume={133 1},
It has recently been shown that the degree of alignment of macromolecules in an aqueous dilute liquid crystalline medium of bicelles is sufficient to permit accurate values of residual 15N-1H, 13C-1H, and 13Calpha-C' dipolar couplings to be obtained on a routine basis, thereby providing potentially unique long-range structural information. To make use of this information in macromolecular structure determination, the magnitude of the axial and rhombic components of the molecular alignment… 

Figures and Tables from this paper

Graphical analysis of the relative orientation of molecular alignment tensors for a protein dissolved in two different anisotropic media.
This communication has simulated the correlation maps for all possible combinations of the Euler angles, which transform one alignment tensor to the other, and compared them to the experimental data sets reported for labeled human ubiquitin.
Variation of molecular alignment as a means of resolving orientational ambiguities in protein structures from dipolar couplings.
This Communication demonstrates a procedure based on an order tensor analysis that completely removes degeneracy in fragment orientations by combining residual dipolar coupling measurements from two alignment media.
De novo determination of internuclear vector orientations from residual dipolar couplings measured in three independent alignment media
This work has developed a protocol which allows the requirement for prior structural knowledge to be dispensed with as long as RDC measurements can be made in three independent alignment media, and shows that complications arising from the existence of multiple solutions can be overcome by careful consideration of alignment tensor magnitudes.
Application of Correlated Residual Dipolar Couplings to the Determination of the Molecular Alignment Tensor Magnitude of Oriented Proteins and Nucleic Acids
An extended histogram method (EHM) is presented which extracts accurate knowledge of the magnitude (Da) and rhombicity (R) of the molecular alignment tensor, A, more effectively from dipolar coupling data.
Explicit treatment of force contribution from alignment tensor using overdetermined linear equations and its application in NMR structure determination
A novel approach has been developed to efficiently extract structural information from RDC by successive application of singular value decomposition (SVD) method in the course of NMR structure determination, illustrated by showing that RDC restraints alone can restore a distorted β‐hairpin to native‐like structure using the replica‐exchange molecular dynamics simulations.
Determination of the Structures of Symmetric Protein Oligomers from NMR Chemical Shifts and Residual Dipolar Couplings
An automated method for determining the solution structures of oligomeric systems using only chemical shifts, sparse NOEs, and domain orientation restraints from residual dipolar couplings (RDCs) without a need for a previously determined structure of the monomeric subunit is presented.
Assessment of molecular structure using frame-independent orientational restraints derived from residual dipolar couplings
It is demonstrated that dipolar couplings can be used to derive a comprehensive set of pairwise angular restraints that do not depend on the orientation of the alignment tensor principal axes, which could prove important for the success of DC-based structure calculations.
De novo determination of protein structure by NMR using orientational and long-range order restraints.
The structure calculation protocol, developed using specific models to describe the novel constraint interactions, is robust, requiring no precise a priori estimation of the various interaction strengths, and provides unambiguous convergence based only on the value of the target function.


Direct structure refinement against residual dipolar couplings in the presence of rhombicity of unknown magnitude.
A simple calculational strategy is presented that makes use of simulated annealing refinement against the residual dipolar couplings in combination with a grid search, to simultaneously refine the structures and ascertain the magnitude of the axial and rhombic components of the tensor.
Direct measurement of distances and angles in biomolecules by NMR in a dilute liquid crystalline medium.
The approach promises to improve the accuracy of structures determined by NMR, and extend the size limit, and distances and angles derived from dipolar couplings in human ubiquitin are in excellent agreement with its crystal structure.
Use of dipolar 1H–15N and 1H–13C couplings in the structure determination of magnetically oriented macromolecules in solution
The resulting residual dipolar couplings contain information on the orientation of the internuclear vectors relative to the molecular magnetic susceptibility tensor, thereby providing information on long range order that is not accessible by any of the solution NMR parameters currently used in structure determination.
Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity
A new approach to the interpretation of nuclear magnetic resonance relaxation experiments on macromolecules in solution is presented. This paper deals with the theoretical foundations and establishes
Accurate Bond and Angle Parameters for X-ray Protein Structure Refinement
Bond-length and bond-angle parameters are derived from a statistical survey of X-ray structures of small compounds from the Cambridge Structural Database. The side chains of the common amino acids
Rotational diffusion anisotropy of proteins from simultaneous analysis of 15N and 13Cα nuclear spin relaxation
Theoretical and experimental results for calbindin D9k,granulocyte colony stimulating factor, and ubiquitin, three proteins with different distributions of N-H and Cα-Hα bond vectors, are used to illustrate the advantages of theultaneous utilization of 13Cα and 15N relaxation data.
Nuclear magnetic dipole interactions in field-oriented proteins: information for structure determination in solution.
The measurement of dipolar contributions to the splitting of 15N resonances of 1H-15N amide pairs in multidimensional high-field NMR spectra of field-oriented cyanometmyoglobin is reported and implications as an additional source of information for protein structure determination in solution are discussed.
The high-resolution, three-dimensional solution structure of human interleukin-4 determined by multidimensional heteronuclear magnetic resonance spectroscopy.
The high-resolution three-dimensional solution structure of recombinant human interleukin-4 (IL-4), a protein of approximately 15 kDa which plays a key role in the regulation of B and T lymphocytes,