Classification of intramolecular side-chain hydrogen bonds in coil fragments of globular proteins

球状蛋白卷曲片段中分子内侧链氢键的分类

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Abstract

The Coil Library, which contains structural data on protein fragments from non-secondary structure regions (coil fragments) of globular proteins, has served as a structural model for denatured proteins and intrinsically disordered proteins. Previously, the hydrogen bonds (HBs) between main-chain atoms in coil fragments were analyzed in detail concerning the number of restricted residues and the dihedral angle distributions of the restricted residues. However, there are few reports on HBs involving side-chain atoms in coil fragments. Herein, I examined and classified HB patterns in 71,134 coil fragments (6-25 residues) from 11,670 proteins in the Protein Data Bank (PDB). I found that 47.4% of the HBs in the coil fragments were formed between atoms from the main chain and the side chain, while 9.1% were between side chains. Although structural motifs containing multiple HBs were observed, 80% of the motifs contained only one or two HBs, referred to as the 1-HB motif and 2-HB motif, respectively. Among the 1-HB motifs, I identified a high probability of motifs whose HB patterns resemble those of standard turns: an HB acceptor atom from the main chain in standard turns is replaced by a polar atom from a side chain in the 1-HB motifs. While motifs resembling β-turns have been previously reported in proteins, including secondary structures, motifs resembling γ-turns were newly identified in the coil fragments in this study. Among the 2-HB motifs, 38.3% featured one HB forming a β-turn and another independent HB involving a surrounding side chain. Using a 2-HB motif in which a side-chain β-turn coexists with the β-turn as an example, I demonstrated that changes in the fraction of subspecies with the addition of an HB can be qualitatively explained by the distribution of the main-chain dihedral angle. In the future, developing a Coil Library that quantitatively incorporates HB formation is expected to enhance the accuracy of structural analyses of unfolded proteins.

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