Helix-sheet packing in proteins.

The three-dimensional structure of a protein is organized around the packing of its secondary structure elements. Although much is known about the packing geometry observed between alpha-helices and between beta-sheets, there has been little progress on characterizing helix-sheet interactions. We present an analysis of the conformation of alphabeta(2) motifs in proteins, corresponding to all occurrences of helices in contact with two strands that are hydrogen bonded. The geometry of the alphabeta(2) motif is characterized by the azimuthal angle theta between the helix axis and an average vector representing the two strands, the elevation angle psi between the helix axis and the plane containing the two strands, and the distance D between the helix and the strands. We observe that the helix tends to align to the two strands, with a preference for an antiparallel orientation if the two strands are parallel; this preference is diminished for other topologies of the beta-sheet. Side-chain packing at the interface between the helix and the strands is mostly hydrophobic, with a preference for aliphatic amino acids in the strand and aromatic amino acids in the helix. From the knowledge of the geometry and amino acid propensities of alphabeta(2) motifs in proteins, we have derived different statistical potentials that are shown to be efficient in picking native-like conformations among a set of non-native conformations in well-known decoy datasets. The information on the geometry of alphabeta(2) motifs as well as the related statistical potentials have applications in the field of protein structure prediction.