Discovery of local packing motifs in protein structures

We present a language for describing structural patterns of residues in pro tein structures and a method for the discovery of such patterns that recur in a set of protein structures. The patterns impose restrictions on the spa tial position of each residue, their order along the amino acid chain, and which amino acids are allowed in each position. Unlike other methods for co mparing sets of protein structures, our method is not based on the use of p airwise structure comparisons which is often time consuming and can produce inconsistent results. Instead, the method simultaneously takes into accoun t information from all structures in the search for conserved structure pat terns which are potential structure motifs, The method is based on describi ng the spatial neighborhoods of each residue in each structure as a string and applying a sequence pattern discovery method to find patterns common to subsets of these strings. Finally it is checked whether the similarities b etween the neighborhood strings correspond to spatially similar substructur es. We apply the method to analyze sets of very disparate proteins from the four different protein families: serine proteases, cuprodoxins, cysteine p roteinases, and ferredoxins. The motifs found by the method correspond well to the site and motif information given in the annotation of these protein s in PDB, Swiss-Prot, and PROSITE, Furthermore, the motifs are confirmed by using the motif data to constrain the structural alignment of the proteins obtained with the program SAP. This gave the best superposition/alignment of the proteins given the motif assignment. (C) 1999 Wiley-Liss, Inc.