A non-redundant set of 1154 protein structures from the Protein Data Bank w
as examined with respect to close interactions between C-H-donor and pi -ac
ceptor groups. A total of 31,087 interactions were found to satisfy our sel
ection criteria. Their geometric parameters suggest that these interactions
can be classified as weak hydrogen bonds.
A set of 12 interaction classes were defined based on the division of the d
onors into three groups and the accepters into four groups. These classes w
ere examined separately, and described in detail in each class. Most promin
ent were interactions between aliphatic C-H donors and aromatic pi -accepto
rs and interactions between aromatic C-H donors and aromatic pi -acceptors.
About three-quarters of the Trp-rings, half of all Phe and Tyr-rings and a
quarter of all His-rings were found to be involved as accepters in C-H...
pi -interactions. On the donor side, a preference for aromatic C-H groups w
as observed, but also for the aliphatic side-chains of the long, extended a
mino acid residues Lys, Arg and Met, and the Pro ring.
The average distance between the C-donor and the center-of-mass of the pi -
acceptor was observed to be significantly longer in the 174 protein structu
res determined at >2.5 Angstrom resolution. Also, the distribution is signi
ficantly wider. This resolution dependance suggests that the force fields c
ommonly used for the refinement of protein structures may not be adequate.
C-H... pi -interactions involving aromatic groups either as donor or as acc
eptor groups are found mostly in the interior of the protein. The more hydr
ophilic the participating groups are, the closer to the surface are the int
eractions located.
About 40% of all C-H... pi -interactions occur between amino acid residue s
ide-chains that are separated by nine or less residues in sequence. Depende
nt on the interaction class, different preferences for secondary structure,
residue type and side-chain conformation were observed.
It is likely that the C-H pi -interactions contribute significantly to the
overall stability of a protein. (C) 2001 Academic Press.