BetaSearch: a new method for querying β-residue motifs

We developed a new method for querying β-residue motifs, called BetaSearch, which leverages the natural planar constraints of β-sheets by indexing them as 2D matrices, thus avoiding much of the computational complexities involved with structural and graph querying. BetaSearch exhibits faster filtering, verification, and overall query time than existing graph indexing approaches whilst producing comparable index sizes. Compared to 3D substructure search methods, BetaSearch achieves 33 and 240 times speedups over index-based and pairwise alignment-based approaches, respectively. Furthermore, we have presented case-studies to demonstrate its capability of motif matching in sequentially dissimilar proteins and described a method for using BetaSearch to predict β-strand pairing.We have demonstrated that BetaSearch is a fast method for querying substructure motifs. The improvements in speed over existing approaches make it useful for efficiently performing high-volume exploratory querying of possible protein substructural motifs or conformations. BetaSearch was used to identify a nearly identical β-residue motif between an entirely synthetic (Top7) and a naturally-occurring protein (Charcot-Leyden crystal protein), as well as identifying structural similarities between biotin-binding domains of avidin, streptavidin and the lipocalin gamma subunit of human C8.The β-sheet is a common secondary structure element that plays important functional and structural roles in proteins, for example, the ligand-binding pockets of biotin-binding proteins and the structure of the commonly-occurring TIM-barrel fold [1]. These processes are often mediated by interactions between adjacent pairs of residues across β-strands. These include the disulphide, ionic, and hydrogen bonds; and hydrophobic packing interactions frequently involved in maintaining the structural stability of a protein or in enzymatic active sites [1]. The influence of pairwise interactions within β-sheets and their terti