Brenda, Generally speaking it is not abnormal to at least *hope* for co-crystals to appear at or around the condition(s) where the native crystals are grown. Therefore many people in fact begin looking for co-crystals by screening a fine grid around the expected crystallization conditions for the apo- protein. It is useful to remember those early crystallization hits that were never followed up - often the co-crystals will pop up in those, instead of the 'main' crystallization hit, so if you remember these early hits you may be able to spare yourself the expense and tedium of a complete re-screen.
Now, having said this I also would like to add that it is also quite likely to get co-crystals to grow in other (sometimes completely unrelated) conditions. Depending on the number of ligands under consideration and on protein supply you may or may not be able to do a full re-screen with each ligand. In pharma we often have to co-crystallize with dozens (and sometimes hundreds) of compounds during the course of a project and we tend to pick up patterns of crystallization preferences based on compound class and/or geometry. Finally, it helps to remember that some protein/ligand combinations may not (easily, or ever) crystallize. In several cases that I can think of we had to use cross-soaking, different protein versions, or analogous (but different!) compounds in order to get the structure. In one recent case I had a situation where the protein would only crystallize if the ligand occupied one of the two binding sites in a homodimer. The other site was occupied by sulfate. This was pure serendipity - by luck my ligand and sulfate concentrations were just right - when I purposefully shifted the ratio either way, the crystals grew worse and eventually did not grow at all. Good luck, Artem -----Original Message----- From: CCP4 bulletin board [mailto:[EMAIL PROTECTED] On Behalf Of Brenda Patterson Sent: Tuesday, January 22, 2008 2:33 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Cocrystals - should they pop up under native conditions? Hello all, I am expecting a somewhat homogeneous reply to this one, but that is fine and welcomed as are anecdotal experiences. I am running co crystallisation experiments and have thus far been trying under oil screens with some success (i.e. various hits in various conditions resulting in crystal growth). These conditions have varied from the native condition up until now. I have recently peered at some fairly old plates I set up under hanging drop under native conditions when running a co crystal trial and have found crystals. Their morphology is very similar to the 'native' form. I bit punier than them if I had to push. So, 1. Should I be surprised that co crystals pop up under native conditions or does it entirely depend on the ligand? 2. Is it probably not going to be a co crystal as usually they don't pop up under native conditions? 3. It totally depends and if I don't like it then I should get out of this beautiful game? I am going to shoot them either way, but just thought I would ask. cheers Brenda
