Efficient and accurate estimation of relative order tensors from λ-maps

Abstract

The rapid increase in the availability of RDC data from multiple alignment media in recent years has necessitated the development of more sophisticated analyses that extract the RDC data’s full information content. This article presents an analysis of the distribution of RDCs from two media (2D-RDC data), using the information obtained from a λ-map. This article also introduces an efficient algorithm, which leverages these findings to extract the order tensors for each alignment medium using unassigned RDC data in the absence of any structural information. The results of applying this 2D-RDC analysis method to synthetic and experimental data are reported in this article. The relative order tensor estimates obtained from the 2D-RDC analysis are compared to order tensors obtained from the program REDCAT after using assignment and structural information. The final comparisons indicate that the relative order tensors estimated from the unassigned 2D-RDC method very closely match the results from methods that require assignment and structural information. The presented method is successful even in cases with small datasets. The results of analyzing experimental RDC data for the protein 1P7E are presented to demonstrate the potential of the presented work in accurately estimating the principal order parameters from RDC data that incompletely sample the RDC space. In addition to the new algorithm, a discussion of the uniqueness of the solutions is presented; no more than two clusters of distinct solutions have been shown to satisfy each λ-map.

Dynafold: A Dynamic Programming Approach to Protein Backbone Structure Determination From Minimal Sets of Residual Dipolar Couplings

“…The first obstacle encountered in this approach is that determination of the optimal order tensor for the protein cannot be expressed recursively. Fortunately, recent introduction of the methods of a priori order tensor estimation in 54,55 can address this issue. In practice, the order tensors produced by these methods are known to be of sufficiently high quality for protein structure determination 36 .…”

Rapid identification of protein–protein interfaces for the construction of a complex model based on multiple unassigned signals by using time-sharing NMR measurements

“…It indicates that the direct utilization of the information, which was obtained using our rapid experimental approach, was successful for the docking study. It would be possible to further improve the accuracy of the prediction by utilizing structural parameters derived from RDC (Miao et al, 2008;Mukhopadhyay et al, 2009), because the parameters provide information of the relative orientation of each protein, although additional time would be required to conduct these experiments.…”

Simultaneous structure and dynamics of a membrane protein using REDCRAFT: Membrane-bound form of Pf1 coat protein

“…Residual dipolar coupling (RDCs) data have been used extensively in recent years for structural studies of a broad range of macromolecules, including globular proteins [7–13], membrane proteins [14; 15], nucleic acids [16–20], and carbohydrates [21–24]. They have also been used to provide insights into the internal dynamics of protein structures [3; 25; 26].…”

“…Other software packages like Xplor-NIH [6], CNS [46], or CYANA [47] are capable of using RDCs during the process of structure determination, however, they rely on an accurate a priori estimate of the order parameters (S xx , S yy , S zz or Da/R). The estimate is often obtained from an unrefined NOE based structure, although recent developments have enabled the calculation of order tensors in the absence of assignment or an initial structure [14; 48]. This process for structure determination uses a single order tensor that applies to the whole molecule, which imposes the assumption that the entire protein is rigid.…”