I study proteins in solution, using mainly small angle X-ray scattering (SAXS). SAXS gives us low-resolution information about the protein structure compared to MX, but allows for investigations of proteins with flexible domains or flexible linker regions. One complication of modeling SAXS data is, however, that one not only needs to calculate the signal from the protein, but also from the hydration shell of the protein. Historically, the hydration shell has been modelled as a continuous envelope around the protein 3-5 Å wide with an excess (electron) density of 10%. This is being challenged now (see e.g. https://www.sciencedirect.com/science/article/pii/S0022283618301232), and there are now also programs that adds explicit waters (https://www.embl-hamburg.de/biosaxs/manuals/crysol3.html).
Not being 100% satisfied with simply adding discrete waters uniformly across the protein surface, I have been looking into other ways to add/model the hydration shell. One method is to use quick MD simulations, but this approach is only really possible if one works with rigid proteins – to model flexible proteins, one needs to calculate the scattering from thousands of potential structures. I would die if I had to setup up thousands of MD simulations (and I cannot just pull the confomations from a single trajectory).
I find the SPaDES (Structure Prediction and Design with Explicit Solvent) approach very interesting (https://www.sciencedirect.com/science/article/pii/S0969212617302939). While I understand the program/algorithm was designed for other purposes, I do think it could also be used for better modelling the hydration shell observed with SAXS. Unlike the typical SAXS approaches, it includes an energy scoring so that waters are not just distributed uniformly. At the same time, it is much faster than MD simulations, making in feasible (hopefully) to predict water molecules on a few thousand models.
I have looked on the demos webpage (https://www.rosettacommons.org/demos/latest/demos-by-category) to see if there are any demonstrations on how to use SPaDES for de novo water predictions, but I have not be able to find any. Can any of you point me towards any guides on how to setup up SPaDES?