Thanks for the responses. Yes, my crystal did survive and I can see density for my ligand.
Summary: 1. If the crystal survives, it’s fine. These are just different ways of exposing the crystal to the ligand and do what works. The only issue will be if you don’t see electron density for the ligand in your structure. If you just add ligand to the drop then there is plenty of other precipitate/stuff that could non-specifically bind to the ligand and reduce the amount available to bind the protein in the crystal. So if you don’t see density, it would still be worth soaking a “clean” crystal in the ligand/precipitant solution. 2. It is OK as long as your crystal survives. I do this regularly, or even just add dry compound to the drops directly, usually after adding more reservoir to make the drop a bit bigger. It seems to work fine for some compounds, not for others. It is very empirical. 3. The truth is in the map. Ergo, zap it and rationalize why it worked or not later.
