SoftWAXS: a computational tool for modeling wide-angle X-ray solution scattering from biomolecules

Abstract

This paper describes a computational approach to estimating wide-angle X-ray solution scattering (WAXS) from proteins, which has been implemented in a computer program called SoftWAXS. The accuracy and efficiency of SoftWAXS are analyzed for analytically solvable model problems as well as for proteins. Key features of the approach include a numerical procedure for performing the required spherical averaging and explicit representation of the solute-solvent boundary and the surface of the hydration layer. These features allow the Fourier transform of the excluded volume and hydration layer to be computed directly and with high accuracy. This approach will allow future investigation of different treatments of the electron density in the hydration shell. Numerical results illustrate the differences between this approach to modeling the excluded volume and a widely used model that treats the excluded-volume function as a sum of Gaussians representing the individual atomic excluded volumes. Comparison of the results obtained here with those from explicit-solvent molecular dynamics clarifies shortcomings inherent to the representation of solvent as a time-averaged electron-density profile. In addition, an assessment is made of how the calculated scattering patterns depend on input parameters such as the solute-atom radii, the width of the hydration shell and the hydration-layer contrast. These results suggest that obtaining predictive calculations of high-resolution WAXS patterns may require sophisticated treatments of solvent.

SAXS/SANS on Supercharged Proteins Reveals Residue-Specific Modifications of the Hydration Shell

“…SAXS and SANS have the advantage that the respective contribution of the hydration layer (or shell) to the overall scattering from the macromolecules varies both in magnitude and sign (34). The HS contribution has been implemented in a number of programs to back-calculate SAXS (and, more rarely, SANS) curves from atomic structures, either as a homogeneous shell of a specific thickness (30)(31)(32)35), as grid elements (36,37), as dummy atoms (38,39), as explicit water molecules (40)(41)(42)(43)(44)(45), as a density map (46,47), or by voxelization (48). Accurate description of the HS is essential for the growing field of quasiatomic protein-structure modeling from solution data (34).…”

Accurate small and wide angle x-ray scattering profiles from atomic models of proteins and nucleic acids

“…(12), sometimes improves comparisons between predicted and experimental scattering profiles. 13,54 As pointed out by Moore, 55 the B-factor is only a rough guide to thermal disorder in solution, at least because B-factors are usually obtained from crystallography and are not necessarily comparable to solution scattering. In addition, correlated thermal motions (not modeled by Debye-Waller factors) contribute to scattering in solution.…”

“…[6][7][8][9][10][11][12][13][14][15] Most rely on the simplified models of water to account for the scattering of excluded volume and hydration shell. Crysol, 9 for example, assumes a layer of uniform excess hydration density around the surface of the protein.…”

Anisotropic time-resolved solution X-ray scattering patterns from explicit-solvent molecular dynamics

“…9,10,13,14,16 However, such calculations may face limitations in the wide-angle regime, where the internal structure of water and protein fluctuations become relevant. [31][32][33] In addition, conformational transitions may be subtle, suggesting that side chain and solvent fluctuations must be carefully averaged out before comparing structural models to experimental data. Another disadvantage of simple implicit solvent models is that they require fitting of free parameters associated with the solvation layer and the excluded solvent, thereby reducing the amount of available information.…”