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. 2009 Nov;201(1):25-33.
doi: 10.1016/j.jmr.2009.07.028. Epub 2009 Aug 5.

Improvement and analysis of computational methods for prediction of residual dipolar couplings

Konstantin Berlin  1 , Dianne P O'Leary, David Fushman
Affiliations

Improvement and analysis of computational methods for prediction of residual dipolar couplings

Konstantin Berlin et al. J Magn Reson. 2009 Nov.

Abstract

We describe a new, computationally efficient method for computing the molecular alignment tensor based on the molecular shape. The increase in speed is achieved by re-expressing the problem as one of numerical integration, rather than a simple uniform sampling (as in the PALES method), and by using a convex hull rather than a detailed representation of the surface of a molecule. This method is applicable to bicelles, PEG/hexanol, and other alignment media that can be modeled by steric restrictions introduced by a planar barrier. This method is used to further explore and compare various representations of protein shape by an equivalent ellipsoid. We also examine the accuracy of the alignment tensor and residual dipolar couplings (RDC) prediction using various ab initio methods. We separately quantify the inaccuracy in RDC prediction caused by the inaccuracy in the orientation and in the magnitude of the alignment tensor, concluding that orientation accuracy is much more important in accurate prediction of RDCs.

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Figures

Figure 1
Figure 1
Planar barrier model for molecular alignment.
Figure 2
Figure 2
Convex hull and equivalent ellipsoids for Cyanovirin-N molecule drawn on top of its van der Waals surface. (A) The convex hull around the molecule. (B) The GE ellipsoid representation. (C) The MVE ellipsoid representation. (D) The PCAE ellipsoid representation with no hydration layer included.
Figure 3
Figure 3
Comparison of the predicted vs. experimental 1H15N RDC values for the backbone amides in Cyanovirin-N, using various versions of the molecular alignment tensor derived from PATI. (A) The experimental alignment tensor was derived directly from the experimental data using least squares. (B) The alignment tensor was constructed using the magnitude (eigenvalues) of the experimental alignment tensor and the tensor orientation predicted using PATI program. (C) The alignment tensor was constructed using the orientation (eigenvectors) of the experimental alignment tensor but PATI-predicted magnitude (eigenvalues) of the tensor. (D) The alignment tensor was fully predicted from PATI simulation. The values of the squared Pearson’s correlation coeffcient, r2, and the scale-insensitive quality factor, Qs, are indicated. Similar graphs for the rest of the molecules studied here can be found in the Supplementary Material.
Figure 4
Figure 4
The agreement between RDC values predicted using PATI are those from PALES prediction. Shown are the 1H15N RDCs for all backbone amides for all molecules studied here. The (unscaled) quality factor Q between the two sets of RDC values is 0.05, the RMSD is 0.6 Hz, and the maximum deviation is 1.7 Hz.
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References

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