Accurate and Efficient SAXS/SANS Implementation Including Solvation Layer Effects Suitable for Molecular Simulations

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Small-angle X-ray and neutron scattering (SAXS/SANS) are crucial for studying biomolecular structure and dynamics in solution.
• These contrast-based methods offer insights into both structural properties and solvent-solute interactions.
• Integrating SAXS/SANS with molecular dynamics (MD) simulations requires efficient and accurate forward models.

Purpose of the Study:

• To develop and validate a novel method for calculating SAXS/SANS intensities from coarse-grained molecular dynamics simulations.
• To enable on-the-fly correction for solvation effects without increasing computational cost.
• To demonstrate the utility of this method for refining biomolecular structure and dynamics using experimental SAS data.

Main Methods:

• Developed a coarse-grained model with one bead per amino acid and three beads per nucleic acid.
• Implemented a forward model for calculating SAXS/SANS intensities with on-the-fly solvation corrections.
• Coupled the forward model with MD simulations, using experimental SAS data for restraints.
• Applied the hybrid-resolution small-angle scattering (hySAS) implementation in PLUMED to gelsolin and a UP1-microRNA complex.

Main Results:

• Demonstrated the feasibility of calculating SAXS/SANS intensities using the described coarse-grained approach.
• Showcased the ability to refine conformational ensembles and structures of proteins and nucleic acids.
• Validated the approach using experimental SAXS data for gelsolin and a microRNA complex.

Conclusions:

• The hySAS implementation provides a computationally efficient and accurate method for integrating SAS data with MD simulations.
• This approach facilitates the determination of biomolecular structure and dynamics in solution.
• The method is versatile, applicable to both atomistic and coarse-grained simulations with various restraining strategies.