Prediction of the packing arrangement of strands in β-sheets of globular proteins

Abstract

A method is proposed for predicting the adjacency order in which strands pack in a β-sheet in a protein, on the basis of its amino acid sequence alone. The method is based on the construction of a predicted contact map for the protein, in which the probability that various residue pairs are close to each other is computed from statistically determined average distances of residue pairs in globular proteins of known structure. Compact regions, i.e., portions of the sequence with many interresidue contacts, are determined on the map by using an objective search procedure. The proximity of strands in a β-sheet is predicted from the density of contacts in compact regions associated with each pair of strands. The most probable β-sheet structures are those with the highest density of contacts. The method has been tested by computing the probable strand arrangements in a five-strand β-sheet in five proteins or protein domains, containing 62–138 residues. Of the theoretically possible 60 strand arrangements, the method selects two to eight arrangements as most probable; i.e., it leads to a large reduction in the number of possibilities. The native strand arrangement is among those predicted for three of the five proteins. For the other two, it would be included in the prediction by a slight relaxation of the cutoff criteria used to analyze the density of contacts.