Propensities of Polar and Aromatic Amino Acids in Noncanonical Interactions: Nonbonded Contacts Analysis of Protein-Ligand Complexes in Crystal Structures Yumi N. Imai, Yoshihisa Inoue, and Yoshio Yamamoto J. Med. Chem. 2007, 50, 1189-1196
Looking at a protein-ligand complex, it is quite easy to spot any hydrogen bonding interactions. This paper examines so-called ‘noncanonical’ interactions, i.e. pretty much all other non-bonded interactions between a protein and a ligand. The authors have analysed the PDB (or rather the tidied up version of the PDB in Relibase+) looking for these noncanonical interactions. The results are divided up per protein amino acid involved. There is much discussion of pi interactions, as well as interactions where the C-H bond acts as a ‘hydrogen-bond’ donor.
The most interesting results of all concern cases of very rare interactions, some of which they are not sure how/why they occur. Are these artefacts, or are they real? The authors make the point that the resolution of the proteins involved were quite good, but I think it would have been useful to further analyse these cases and to see whether these interactions are ‘forced’ by the presence of other favourable interactions, or whether that area of the protein was quite flexible. It would also have been nice to get some idea of how common the various interactions are with respect to each other; although there are some percentages mentioned in the text the figures are not complete, and there is some confusion over whether a particular percentage refers to the overall number of interactions, or just the noncanonical interactions.
All in all, a paper that provides useful qualitative information on the sorts of noncanonical interactions that occur in proteins. These data may inspire the development of new terms for docking functions, which typically concentrate on hydrogen bonding and lipophilic interactions.
