MetalS3, a database-mining tool for the identification of structurally similar metal sites

AbstractWe have developed a database search tool to identify metal sites having structural similarity to a query metal site structure within the MetalPDB database of minimal functional sites (MFSs) contained in metal-binding biological macromolecules. MFSs describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. Such a local environment has a determinant role in tuning the chemical reactivity of the metal, ultimately contributing to the functional properties of the whole system. The database search tool, which we called MetalS3 (Metal Sites Similarity Search), can be accessed through a Web interface at http://metalweb.cerm.unifi.it/tools/metals3/. MetalS3 uses a suitably adapted version of an algorithm that we previously developed to systematically compare the structure of the query metal site with each MFS in MetalPDB. For each MFS, the best superposition is kept. All these superpositions are then ranked according to the MetalS3 scoring function and are presented to the user in tabular form. The user can interact with the output Web page to visualize the structural alignment or the sequence alignment derived from it. Options to filter the results are available. Test calculations show that the MetalS3 output correlates well with expectations from protein homology considerations. Furthermore, we describe some usage scenarios that highlight the usefulness of MetalS3 to obtain mechanistic and functional hints regardless of homology.

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