Fast-SAXS-pro: A unified approach to computing SAXS profiles of DNA, RNA, protein, and their complexes

Jan. 11, 2013

A generalized method, termed Fast-SAXS-pro, for computing small angle x-ray scattering (SAXS) profiles of proteins, nucleic acids, and their complexes is presented. First, effective coarse-grained structure factors of DNA nucleotides are derived using a simplified two-particle-per-nucleotide representation. Second, SAXS data of a 18-bp double-stranded DNA are measured and used for the calibration of the scattering contribution from excess electron density in the DNA solvation layer. Additional test on a 25-bp DNA duplex validates this SAXS computational method and suggests that DNA has a different contribution from its hydration surface to the total scattering compared to RNA and protein. To account for such a difference, a sigmoidal function is implemented for the treatment of non-uniform electron density across the surface of a protein/nucleic-acid complex. This treatment allows differential scattering from the solvation layer surrounding protein/nucleic-acid complexes. Finally, the applications of this Fast-SAXS-pro method are demonstrated for protein/DNA and protein/RNA complexes.

Figure Derivation of coarse-grained DNA structure factors. (Left) A simplified two-bead representation of each DNA nucleotide, where one bead (in blue) represents the sugar-phosphate backbone group and the other (in red) the base side-chain group. The atoms colored in blue and red are selected to represent the positioning of each simplified group, based on their center-of-scattering as defined in Eq. ( 3 ). Their structure factors are shown on the bottom for both backbone and base groups. For comparison, structure factors and the positions of RNA nucleotides are also shown on the right.

Results from: Krishnakumar M. Ravikumar, Wei Huang, and Sichun Yang Journal of Chemical Physics,138, 024112 (2013); doi: 10.1063/1.4774148 .