WAXS in Solvent (WAXSiS) computes small- and wide-angle X-ray scattering curves based on explicit-solvent all-atom molecular dynamics simulations.

About WAXSiS

WAXSiS: Wide Angle X-ray Scattering in Solvent

WAXSiS is an automated web server that computes Small- and Wide-Angle X-ray Scattering (SAXS/WAXS, or SWAXS) curves of biomolecules in solution. The calculations are based on explicit-solvent all-atom molecular dynamics (MD) simulations. If you use results from WAXSiS for a publicaiton, we kindly request that you cite these articles:

Po-chia Chen and Jochen S. Hub
Validating solution ensembles from molecular dynamics simulations by wide-angle X-ray scattering data
Biophys. J., 107, 435-447 (2014)  

Christopher J. Knight and Jochen S. Hub
WAXSiS: a web server for the calculation of SAXS/WAXS curves based on explicit-solvent molecular dynamics
Nucleic Acids Res., 43, W225-W230 (2015)  

How does WAXSiS work?

WAXSiS runs a short explicit-solvent MD simulation using YASARA, typically with a length between 15 and 250 picoseconds. During the simulation, all backbone atoms of protein/DNA/RNA as well as all heavy atoms of cofactors/ligands are restrained by a harmonic potential. That procedure ensures that the biomolecule samples only conformations similar to the input structure. After the simulation has finished, a spatial envelope is constructed that includes the biomolecule and its solvation shell at a distance of 7Å from the biomolecule atoms. The excluded-solvent scattering is computed based on a pure-water simulation that was conducted previously. The SAXS/WAXS curve is computed following the calculation described in the papers.

How does WAXSiS compare to other web servers that compute SAXS curves?

  • The most important difference is that WAXSiS uses explicit solvent, described through a force field-based molecular dynamics simulation. Hence, the solvation shell is described (a) in atomic detail and (b) including thermal fluctutations. Importantly, because the MD simulation reproduces the structure and density of the solvation layer, no fitting of the solvation shell is required to match the experimental data. The same is true for the excluded solvent contribution.
  • The MD simulations naturally include thermal fluctuations also for atoms of the biomolecule, which are relevant at wider angles.
  • The fitting procedure uses only two fitting parameters: (a) the overall scale, which is anyway arbritrary; and (b) a constant offset to (partly) absorp experimental uncertainties due the buffer subtraction (and possibly dark currents). Because the calculated SWAXS curve does not contain any free parameters, we fit the experimental curve to the calculated curve and not vice versa. In contrast to methdos based on the implicit solvent method, WAXSiS does not require any solvent-related fitting parameters such as the density of the hydration layer, overall excluded solvent, or scaling parameters for dummy atoms. (Dummy atoms are used by implicit-solvent methods for the buffer subtraction).

More details on the MD simulation

The MD simulation frames are generated by the YASARA software. Given a PDB file of a biomolecule (protein, RNA, and/or DNA), the biomolecule is placed into a cuboid simulation box, and the box is filled with explicit water and counter ions. No additional salt is added, because the positions of ions would be sampled too slowly compared to the length of the MD simulation. Protein and nucleotide atoms are described by the AMBER03 force field, and the TIP3P water model is adopted for water. Modified amino acids and cofactors are parameterized using YASARA's AUTOSMILES procedure (AM1-BCC charges and GAFF atom types). Backbone atoms and heavy atoms of ligands are position-restrained (force constant 1000 kJ mol-1nm-2). After a careful energy minimization, a short MD simulation is conducted, and the coordinates are written every 0.5 picoseconds. The first 5% of the MD simulation are removed for equilibration (but at least 3ps and at most 20ps). All remaining frames are used for the subsequent calculation of the SWAXS curve.

The required length of the simulation strongly depends on the size of the biomolecule: the smaller the biomolecule, the more simulation frames are required to arrive at a converged SWAXS curve. The number of frames are computed using the formula 2e5/N-0.77, where N is the (approximate) number of atoms in the envelope. Hence, the simulation time may vary between roughly 10 and 250 picoseconds. The number of simulations frames is listed in the output notes.

How does WAXSiS deal with unusual atoms, such as exotic metal ions?

Simulation parameters are available for common metal ions, such as for elements K, Na, Rb, Ca, Mg, Fe, Mn, Zn etc. However, the PDB lists numerous structures that contain exotic metal ions, for which no simulation parameters are available. Therefore, we replace such exotic ions by iron only during the MD simulation. For the SWAXS calculation, the simulated iron ion will treated as the exotic metal ion, so the correct atomic structure factor (and correct number of electrons) enters the SWAXS curve. Only the distribution of atoms in the very vicinity of the exotic ion is slightly affected. This approximation has only a very small effect on your SWAXS curve if you don't have many exotic ions in your structure. Note that some exotic non-metal elements cannot currently be processed. These are detailed in the Help section.

WAXSiS updates and bug fixes

2016, Sept 18: In case that the MD simulation hangs, the jobs is now killed after 48 hours. This may happen if the many bond lengths in the uploaded PDB file are unphysical as a consequence of some modelling. In such cases, Yasara tries to derive many force field parameters of many unphysical molecules, which might take forever.

2015, May 20: Default for option Buffer Subtraction is now Total buffer scattering subtracted.

2015, May 20: Fixed issue that Ca2+ was incorrectly considered as an exotic metal atom and therefore replaced with Fe2+ in the simulation (but not in the SAXS calculation).

2015, May 28: If the simulation explodes due to atomic clashes, WAXSiS does not stop in error but instead reruns the simulation with frozen solute coordinates. A note with explanations is added to the email and to the notes output.

2015, May 28: Updated Yasara to avoid an error caused by PDB files not following PDB conventions (using multiple models instead of multple chains, as sometimes found in biological units).

2015, June 23: The number of surface elemnts of the envelope is not any more fixed to 5120, but increased in case of a large solute. This fixes an issue that may occur with very long solutes.

2015, August 28: Fixed a bug possibly introduced on May 28: If the simulation box explodes in a normal position-restrained simulation, we redo the simulation with a constrained solute. However, we may by accident have frozen all atoms (including water) in such cases. So if your calculation was based on a frozen solute, better redo the calculation. This is reported in the notes.log and in the notification e-mail.

2016, April 6: Added pure-water boxes up to 70nm length. To save memory, pure-water boxes longer than 40nm are cuboids with a cross section area 30nm x 30nm. Hence, long solutes with a length of up to 70nm are supported, but not spherical solutes up to a diameter of 70nm. Please contatct us if this limitation causes any trouble. In addition, increased the minimum value for the parameter J to 500 (was 100 before).

Privacy & Cookies

WAXSiS optionally allows you to provide an email address when submitting jobs. This address is used to notify you on job completion, and is also the means of verification for cancelling your own queued jobs if required. We may also contact you directly by email in case we notice any issues with your submissions. Your email is not used for any other purpose.

Other users will not have access to your results, even if they know your job ID. The results page for a job is only accessible online using a randomised URL which is presented to you. It is up to you if you wish to share this URL with others within the 28 day expiry period. Results can also be downloaded in .tar.gz format from this results page.

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