I’ll be honest I thought I knew a fair bit about small
molecules binding to proteins. If someone asked me what a phenyl ring in a
molecule was doing I could talk earnestly about the entropic effect of
displacing those water molecules, stacking interactions, Van der Waals forces,
maybe even pi-charge interactions. I could have also talked about
hydrogen-bonding and I would have certainly mentioned the hydrophobic effect
(mind you that is more complicated than it looks sometimes) and how a molecule
rotates (i.e. the less carbon chains and more rings the better).
One thing I certainly would not have mentioned was how
individual bonds vibrate, but what do I know? 2 recent papers talking about
deuterium effecting how compounds smell and another using the IR spectra of nitrile
groups to explain the observed binding affinity of a family of HIV drugs demonstrate how what I think I know and what I actually know are sometimes a
disappointing distance apart.
