Dear Simon, DMSO concentrations lower than 5% usually do not alter crystallizability of a protein. In case you want to avoid this solvent may I suggest you trying out two methods that worked for me.
1. If you grow crystals in PEGs or similar molecules you might try to solubilize the compound in a small amount of precipitant solution. This is helpful if you want just a 1:4 protein:ligand ratio. 2. Sometimes solubility is low even in 5% DMSO (or diluted solutions of glycerol, alcohols and similar molecules). In these cases setting up drops in the presence a saturated solution and some precipitate of the compound may also lead to good co-crystals. As one molecule passes from the saturated solution to the bound state, a new molecule is solubilized from the precipitate, which gradually dissolves and passes from the solution to its binding site in the protein. Indeed, this sounds like a soaking experiment and it works well if the compound is coloured, so that you can see if the crystals actually become of the same colour. Just remember to wash them thoroughly before measurements, in order to remove traces of the ligand precipitate that would result in bad diffraction pattern. Hope this will help you. Marco
