Combination of coarse-grained molecular dynamics simulations and small-angle X-ray scattering experiments.

The combination of molecular dynamics (MD) simulations and small-angle X-ray scattering (SAXS), called the MD-SAXS method, is efficient for investigating protein dynamics. To overcome the time-scale limitation of all-atom MD simulations, coarse-grained (CG) representations are often utilized for biomolecular simulations. In this study, we propose a method to combine CG MD simulations with SAXS, termed the CG-MD-SAXS method. In the CG-MD-SAXS method, the scattering factors of CG particles for proteins and nucleic acids are evaluated using high-resolution structural data in the Protein Data Bank, and the excluded volume and the hydration shell are modeled using two adjustable parameters to incorporate solvent effects. To avoid overfitting, only the two parameters are adjusted for an entire structure ensemble. To verify the developed method, theoretical SAXS profiles for various proteins, DNA/RNA, and a protein-RNA complex are compared with both experimental profiles and theoretical profiles obtained by the all-atom representation. In the present study, we applied the CG-MD-SAXS method to the Swi5-Sfr1 complex and three types of nucleosomes to obtain reliable ensemble models consistent with the experimental SAXS data.