Purification of ACVR1 for co-crystallisation with new compounds and for fragment screening crystals

I was away on leave last week, but happily, before I left, I set up 25 crystal plates of ACVR1 with various compounds. The details of the protein purification, the compounds used and some of the crystals obtained are here, on Zenodo. So I was able to at least come back to something after my holiday.

I got loads and loads of beautiful crystals for ACVR1 with LDN-193189, which I’m using for the fragment screening. The crystals (or, in most cases, crystalline precipitate) for the other compounds are not that great, but there are a few I could mount, so I will do so and send them to the synchrotron next week. Many of my fine screens haven’t worked, with no crystals growing at all. I think this is because of a couple of things: the conditions in the wells aren’t always that clear – for example, there is sodium malonate in one of the hits I got, but the pH isn’t specified in the screen conditions. Also, I have sometimes had to change pH or volumes of components because of limits on the volumes that can be pippetted by the liquid handler. And occasionally we don’t have exactly the same component in stock as is required by the screen. Nevertheless, I have mainly screened precipitant concentrations so far, so it is still possible to do some more fine screening varying pH or salt concentrations, so this is what I’ll be doing in the next few weeks.


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