title: Discovery of a significant, nontopological preference for antiparallel alignment of helices with parallel regions in sheets.
abstract: To help elucidate the role of secondary structure packing preferences in protein folding, here we present an analysis of the packing geometry observed between alpha-helices and between alpha-helices and beta-sheets in 1316 diverse, nonredundant protein structures. Finite-length vectors were fit to the alpha-carbon atoms in each of the helices and strands, and the packing angle between the vectors, Omega, was determined at the closest point of approach within each helix-helix or helix-sheet pair. Helix-sheet interactions were found in 391 of the proteins, and the distributions of Omega values were calculated for all the helix-sheet and helix-helix interactions. The packing angle preferences for helix-helix interactions are similar to those previously observed. However, analysis of helix-strand packing preferences uncovered a remarkable tendency for helices to align antiparallel to parallel regions of beta-sheets, independent of the topological constraints or prevalence of beta-alpha-beta motifs in the proteins. This packing angle preference is significantly diminished in helix interactions involving mixed and antiparallel beta-sheets, suggesting a role for helix-sheet dipole alignment in guiding supersecondary structure formation in protein folding. This knowledge of preferred packing angles can be used to guide the engineering of stable protein modules.
authors.affiliation: Department of Biochemistry and Molecular Biology and Center for Biological Modeling, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Hespenheide
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Kuhn
mesh_terms: D030562:Databases, Protein; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary