Interactions in Proteins: A Structural Bioinformatics Study
Interactions in Proteins: A Structural Bioinformatics Study
1Structural Biology / Crystallography,
2 Biocomputing,
Institut für Molekulare Biotechnologie (IMB),
Beutenbergstr. 11,
D-07745 Jena / Germany
# Novartis Pharma AG,
Klybeckstr. 141,
CH-4057 Basel / Switzerland
* Sercon GmbH,
Anna-Birle-Str. 11,
D-55252 Mainz-Kastel / Germany
A non-redundant set of 1154 protein structures from the Protein Data Bank was examined with respect to close interactions between C-H-donor and p-acceptor groups [1]. A total of 31,087 interactions were found to satisfy the geometrical selection 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 donors into three groups and the acceptors into four groups. These classes were examined separately, and the respective interaction described in detail in each class. Most prominent were interactions between aliphatic C-H donors and aromatic p-acceptors and interactions between aromatic C-H donors and aromatic p-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 acceptors in C-H...
-interactions. On the donor side, a preference for aromatic C-H groups was observed, but also for the aliphatic side-chains of the long, extended amino acid residues Lys, Arg and Met, and the Pro ring. The average distance between the C-donor and the center-of-mass of the p-acceptor was observed to be significantly longer in the 174 protein structures determined at >2.5 Å resolution. Also, the distribution is significantly wider. This resolution dependence suggests that the force fields commonly used for the refinement of protein structures may not be adequate. C-H...-interactions involving aromatic groups either as donor or as acceptor groups are found mostly in the interior of the protein. The more hydrophilic the participating groups are, the closer to the surface are the interactions located. About 40 % of all C-H...-interactions occur between amino acid residue side-chains that are separated by nine or less residues in sequence. Dependent on the interaction class, different preferences for secondary structure, residue type and side-chain conformation were observed. It is likely that the C-H...-interactions contribute significantly to the overall stability of a protein.
These results foster a newly emerging general concept of hydrogen bonding in biopolymers, which not only involves N-H and O-H as donor groups, but also C-H, and not only N and O as acceptor groups, but also -systems. We postulate that the incorporation of the entirety of these interactions leads to a more complete description of biopolymer structure, stability and function, and that this may provide new perspectives and possibly new answers [2].