WAXSiS: a web server for the calculation of SAXS/WAXS curves based on explicit-solvent molecular dynamics

Abstract

Small- and wide-angle X-ray scattering (SWAXS) has evolved into a powerful tool to study biological macromolecules in solution. The interpretation of SWAXS curves requires their accurate predictions from structural models. Such predictions are complicated by scattering contributions from the hydration layer and by effects from thermal fluctuations. Here, we describe the new web server WAXSiS (WAXS in solvent) that computes SWAXS curves based on explicit-solvent all-atom molecular dynamics (MD) simulations (http://waxsis.uni-goettingen.de/). The MD simulations provide a realistic model for both the hydration layer and the excluded solvent, thereby avoiding any solvent-related fitting parameters, while naturally accounting for thermal fluctuations.

Figure 1.

Construction of the hydration layer and excluded solvent using a spatial envelope. (A) The envelope is built from an icosphere (A′), which is obtained from a regular isosahedron by recursively subdividing is triangular faces into smaller triangles. Subsequently, the envelope is by default constructed at a distance of 7 Å from all solute atoms of all simulation frames (A''). (B) The hydration layer (left) and the excluded solvent (right) are obtained as the atoms inside of the envelope, overlayed with the solute or pure-solvent simulation system, respectively.

Figure 2.

Workflow of a WAXSiS job. Orange boxes indicate user input, blue boxes indicates workflow conducted by YASARA and red boxes other WAXSiS workflow.

Figure 3.

(A) SWAXS curves computed by WAXSiS for a number of proteins, as listed in the legend, computed from PDB structures 1ier, 1mnz, 1lys, and 1d3z. Red curves show fitted experimental data, taken from the Small Angle Scattering Biological Data Bank (26) (SASDA82 and SASDAK6) and from (12). (B–E) Molecular representations of solute and hydration layer. The envelope (orange) is clipped for visualization. (B) Apoferritin, together with its envelope with a hole at the center, (C) glucose isomerase, (D) lysozyme, (E) ubiquitin.