PackHelix: a tool for helix-sheet packing during protein structure prediction.

The three-dimensional structure of a protein is organized around the packing of its secondary structure elements. Predicting the topology and constructing the geometry of structural motifs involving α-helices and/or β-strands are therefore key steps for accurate prediction of protein structure. While many efforts have focused on how to pack helices and on how to sample exhaustively the topologies and geometries of multiple strands forming a β-sheet in a protein, there has been little progress on generating native-like packings of helices on sheets. We describe a method that can generate the packing of multiple helices on a given β-sheet for αβα sandwich type protein folds. This method mines the results of a statistical analysis of the conformations of αβ(2) motifs in protein structures to provide input values for the geometric attributes of the packing of a helix on a sheet. It then proceeds with a geometric builder that generates multiple arrangements of the helices on the sheet of interest by sampling through these values and performing consistency checks that guarantee proper loop geometry between the helices and the strands, minimal number of collisions between the helices, and proper formation of a hydrophobic core. The method is implemented as a module of ProteinShop. Our results show that it produces structures that are within 4-6 Å RMSD of the native one, regardless of the number of helices that need to be packed, though this number may increase if the protein has several helices between two consecutive strands in the sequence that pack on the sheet formed by these two strands. Published 2011 Wiley-Liss, Inc.