Anyone expecting new medicines to spring out of Zeus's forehead like Athena, Goddess of Wisdom, will be disappointed. Everything is thanks to someone else, to a lot of someone elses. And others will work on what we did in turn. (10/10

If its an unprecedented target and there's protein NMR I read it with high interest.

Sadly, biophysical evidence of binding to the target of interest is not a pre-requisite for publication.

If water is not in the binding site then what is?

Because a vacuum would be much worse. No vacuums in biological systems.

Yes it’s a good rule of thumb. The reason I put them together is that there is a spectrum entropic and enthalpic energies for waters bound to proteins rather than two discrete categories as your rule of thumb implies.

Thanks Chris, I like your options 1, 2 and 3. I put 1 and 3 together to keep things simple. EG Displacing and replacing I see as the same thing (I call it Replacing) the only thing that varies is your choice of what to replace the water with as you highlight.

Here's the pic

We‘ll save the pi hole til last.