Predicting the Geometry of Metal Binding Sites from Protein Sequence

Metal binding is important for the structural and functional characterization of proteins. Previous prediction efforts have only focused on bonding state, i.e. deciding which protein residues act as metal ligands in some binding site. Identifying the geometry of metal-binding sites, i.e. deciding which residues are jointly involved in the coordination of a metal ion is a new prediction problem that has been never attempted before from protein sequence alone. In this paper, we formulate it in the framework of learning with structured outputs. Our solution relies on the fact that, from a graph theoretical perspective, metal binding has the algebraic properties of a matroid, enabling the application of greedy algorithms for learning structured outputs. On a data set of 199 non-redundant metalloproteins, we obtained precision/recall levels of 75%/46% correct ligand-ion assignments, which improves to 88%/88% in the setting where the metal binding state is known.