Mining Patterns from Protein Structures

Wei Wang, University of North Carolina at Chapel Hill, USA

Abstract

One of the next great frontiers in molecular biology is to understand, and predict protein function. Proteins are simple linear chains of polymerized amino acids (residues) whose biological functions are determined by the three-dimensional shapes that they fold into. Hence, understanding proteins requires a unique combination of chemical and geometric analysis. A popular approach to understanding proteins is to break them down into structural sub-components called motifs. Motifs are recurring structural and spatial units that are frequently correlated with specific protein functions. Traditionally, the discovery of motifs has been a laborious task of scientific exploration.
In this talk, I will discuss recent data-mining algorithms for automatically identifying potential spatial motifs. These methods automatically find frequently occurring substructures within graph-based representations of proteins. We represent each protein's structure as a graph, where vertices correspond to residues. Two types of edges connect residues: sequence edges connect pairs of adjacent residues in the primary sequence, and proximity edges represent physical distances, which are indicative of intra-molecular interactions. Such interactions are believed to be key indicators of the protein's function.
This representation allows us to apply innovative graph mining techniques to explore protein databases and associated protein families. The complexity of protein structures and corresponding graphs poses significant computational challenges. The kernel of this approach is an efficient subgraph-mining algorithm that detects all (maximal) frequent subgraphs from a graph database with a user-specified minimal frequency.


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