Hydrogen bonds with π-acceptors in proteins:: Frequencies and role in stabilizing local 3D structures

A comprehensive structural analysis of X-H . . . pi hydrogen bonding in proteins is performed based on 592 published high-resolution crystal structures (less than or equal to 1.6 Angstrom). All potential donors and accepters are considerered, including acidic C-H groups. The sample contains 1311 putative X-H . . . pi hydrogen bonds with N-H, O-H or S-H donors, that is about one per 10.8 aromatic residues. By far the most efficient n-acceptor is the side-chain of Trp, which accepts one X-H . . . pi hydrogen bond per 5.7 residues. The focus of the analysis is on recurrent structural patterns involving regular secondary structure elements. Numerous examples are found where peptide X-H . . . pi interactions are functional in stabilization of helix termini, strand ends, strand edges, beta -bulges and regular turns. Side-chain X-H . . . pi hydrogen bonds are formed in considerable numbers in alpha -helices and beta -sheets. Geometrical data on various types of X--H . . . pi hydrogen bonds are given. (C) 2001 Academic Press.