BioNMR - still aggressively waiting to take off.

Folks, it's that time again. I am planning the #YoungScientistNetworking for Spring. Do you want to share your journey in science (chemistry preferred) with people on social media? If so, DM me. Want to know what this looks like? Check out the hashtag on Twitter or Bluesky.

I continue to be astounded about how many rings there are to choose from for drug design and how many haven't been made yet.

It’s important to be symmetrical in your assessment of both positive and negative data.

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

On this day in 1981, a landmark paper in NEJM described four patients with evidence of immunodeficiency associated with PJP pneumonia, disseminated CMV, and Kaposi sarcoma. The disease would come to be known as HIV/AIDS. Revisit the paper: nej.md/41iekKD

#MedSky #IDSky

Don't forget that water often likes to sit on top of pi systems (part of last week's lecture).

Tonight we'll be getting in to how to build drugs (and of course McConnell's Rule of Two).

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.

What to do with waters in drug discovery is one of the most important decisions that drug designers need to make. What would you do with the FLAP water on HIV protease? Address or Replace?

Average pace of NYC Marathon finishers by age group. Amazing how everyone in the under 60 cohorts is remarkably close together. Source: https://buff.ly/3O1N2jI

Here's the pic

I'll post over the next week or so on H-bonds, especially enthalpically strong H-bonds, but before I do, just a reminder that two thirds of H-bonds that drugs form are actually weak. Check out the McConnellsMedchem post for more.
mcconnellsmedchem.com/2023/06/04/i...

We‘ll save the pi hole til last.

Here's the Six Classes of Molecular Interactions for designing drugs and their frequencies in protein-ligand complexes. They are all very useful in drug design (except perhaps the last one). I'll post a few slides from my Medchem Uni course for each interaction over the coming days/weeks.

For some reason in medicinal chemistry we like to use weight (Daltons) as a measure for atomic and molecular size. The picture below shows why this is hugely misleading for halogens and hydrogen.

Heres the latest post on McConnell’s Medchem. Some medchem atoms are not as big as you think (especially the halogens) mcconnellsmedchem.com/2024/10/07/h...

I have made a ChemSky starter pack and am posting here to help boost visibility. This list is not exhaustive, but should hopefully help newcomers or rejoiners find some accounts and feeds to follow
go.bsky.app/C9BtrLj

Hi Bluesky