Predicting solution scattering patterns with explicit-solvent molecular simulations

Abstract

Small-angle X-ray or neutron scattering (SAXS/SANS/SAS) is widely used to obtain structural information on biomolecules or soft-matter complexes in solution. Deriving a molecular interpretation of the scattering signals requires methods for predicting SAS patterns from a given atomistic structural model. Such SAS predictions are nontrivial because the patterns are influenced by the hydration layer of the solute, the excluded solvent, and by thermal fluctuations. Many computationally efficient methods use simplified, implicit models for the hydration layer and excluded solvent, leading to some uncertainties and to free parameters that require fitting against experimental data. SAS predictions based on explicit-solvent molecular dynamics (MD) simulations overcome such limitations at the price of an increased computational cost. To rationalize the need for explicit-solvent methods, we first review the approximations underlying implicit-solvent methods. Next, we describe the theory behind explicit-solvent SAS predictions that are easily accessible via the WAXSiS web server. We present the workflow for computing SAS pattern from a given molecular dynamics trajectory. The calculations are available via a modified version of the GROMACS simulations software, coined GROMACS-SWAXS, which implements the WAXSiS method. Practical considerations for running routine explicit-solvent SAS predictions are discussed.

Keywords: All-atom molecular dynamics simulations; Excluded solvent; Hydration layer; SANS; SAXS; Small-angle scattering.