Someone prodded me off-channel to make what I said actually intelligible - fair point.

In a sentence:  there exist isocratic solvent mixtures that will both not kill your protein, and solubilise the brickdust you think will only dissolve in toluene, cyclohexane or similar.

Now, finding that mixture is trickier - you will have to resort to esoteric magic like the ancient lost art of Design of Experiments. Knowledge you can only acquire through long and patient study of obscure grimoires <https://portlandpress.com/biochemist/article/46/6/29/235488/A-beginner-s-guide-to-design-of-experiments-for> hidden in deep vaults <https://zenodo.org/records/13998442>.

I jest, of course - but daily I'm amazed at how daft I and (almost) everyone around me are for not using DoE all the time for just about everything.  Certainly crystal optimization, even though Charlie told us how to do it <https://www.sciencedirect.com/science/article/abs/pii/S1046202305801422> more than a generation ago.

But no matter:  a month in the lab will save you an hour in the library.
Frank



On 09/09/2025 22:06, Frank Von Delft wrote:
I discovered recently that real chemists - the hardcore process types - know and love isocratic solvents.  The one I learnt it from, had no trouble quickly  demonstrating why.

So... we've been missing a trick.

(I'm aware this is a slightly more vague answer than you needed.)

Frank

Sent from tiny silly touch screen
------------------------------------------------------------------------
*From:* Gloria Borgstahl <[email protected]>
*Sent:* Tuesday, 9 September 2025 20:55
*To:* [email protected]
*Subject:* [ccp4bb] SMI protein target stall structures

Hello Friends,  I am interested in finding out what protocols people are using to work with SMIs dissolved in 100% DMSO.  What steps do you take to get the compound into the minimal DMSO (2-5%)?  If soaking do you try to get it dissolved into the crystallization reservoir solution?  Thank you!
Asking for a friend,  Gloria

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