Abstract
A fast Fourier transform (FFT) method is described for determining the substructure of anomalously scattering atoms in macromolecular crystals that allows successful structure determination by X-ray single-wavelength anomalous diffraction (SAD). This method is based on the maximum-likelihood SAD phasing function, which accounts for measurement errors and for correlations between the observed and calculated Bijvoet mates. Proof of principle is shown that this method can improve determination of the anomalously scattering substructure in challenging cases where the anomalous scattering from the substructure is weak but the substructure also constitutes a significant fraction of the real scattering. The method is deterministic and can be fast compared with existing multi-trial dual-space methods for SAD substructure determination.
Highlights
Single-wavelength anomalous diffraction (SAD) phasing has become the predominant method to solve novel structures when a molecular-replacement approach is not possible or not sufficient (Hendrickson, 2014)
We describe here an approximation of the maximum-likelihood SAD (MLSAD) target, termed Phassade, that can be calculated by fast Fourier transform (FFT) to generate a set of trial positions starting from a null substructure
Current methods for substructure determination are built upon the estimation of FA, the structure factors of the anomalously scattering atoms, through Pattersons calculated from the square of the coefficients and/or direct methods using the FA estimates directly
Summary
Single-wavelength anomalous diffraction (SAD) phasing has become the predominant method to solve novel structures when a molecular-replacement approach is not possible or not sufficient (Hendrickson, 2014). HySS (GrosseKunstleve & Adams, 2003) modifies the SHELXD algorithm so that the initial oriented two-atom substructures from Patterson analysis are placed in the unit cell with the fast translation function, achieving expansion to three sites by fixing the two-atom substructure and using a second fast translation function to search for a single atom; phase refinement using the tangent formula in reciprocal space is replaced by the related procedure of density squaring in real space. We describe here an approximation of the MLSAD target, termed Phassade (for Phaser anomalous substructure detertermination), that can be calculated by fast Fourier transform (FFT) to generate a set of trial positions starting from a null substructure This method simultaneously tests hypotheses for all potential positions for an anomalous scatterer on a grid covering the unit cell. The Phassade search target retains the strength of the MLSAD target in automatically combining information from both the real and imaginary scattering contributions, and improves on current methods when the anomalous signal is low but the real contribution to the scattering is high, for example when the anomalous scatterer is a metal ion and the wavelength is far from the absorption edge
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