paper of the week: Kuntz et al., PNAS '99

Todays paper of the week is from the late summer of 1999. Better still, is from the University of California... Late 90s, late summer, California - this all sounds marvelous.

I really like papers which start with a question you never thought existed, but it turnes out that it is immediately interesting and even you want to know the answer. So the question here is: what is the maximal possible affinity of a ligand?

The approach of Kuntz and colleagues is simple: they search the literature and plot known affinities (ΔG) vs the number of non-hydrogen atoms for all the tightly biding ligands they can get their hands on.

The trend they get is beautiful: below 15 atoms you get 1.5 kCal per atom, and adding more than 15 atoms does not improve the affinity any more. There are some outliers: metal ions and biotin, for instance. So now we know.

Kuntz, I., Chen, K, Sharp, K, & Kollman, P (1999). The maximal affinity of ligands Proceedings of the National Academy of Sciences, 96 (18), 9997-10002 DOI: 10.1073/pnas.96.18.9997