Structures, basins, and energies: A deconstruction of the Protein Coil Library

Globular proteins adopt complex folds, composed of organized assemblies of alpha-helix and beta-sheet together with irregular regions that interconnect these scaffold elements. Here, we seek to parse the irregular regions into their structural constituents and to rationalize their formative energetics. Toward this end, we dissected the Protein Coil Library, a structural database of protein segments that are neither alpha-helix nor beta-strand, extracted from high-resolution protein structures. The backbone dihedral angles of residues from coil library segments are distributed indiscriminately across the phi,psi map, but when contoured, seven distinct basins emerge clearly. The structures and energetics associated with the two least-studied basins are the primary focus of this article. Specifically, the structural motifs associated with these basins were characterized in detail and then assessed in simple simulations designed to capture their energetic determinants. It is found that conformational constraints imposed by excluded volume and hydrogen bonding are sufficient to reproduce the observed phi,psi distributions of these motifs; no additional energy terms are required. These three motifs in conjunction with alpha-helices, strands of beta-sheet, canonical beta-turns, and polyproline II conformers comprise similar to 90% of all protein structure.