Researchers at MDS Proteomics and the Samuel Lunenfeld Research Institute at Toronto’s Mount Sinai Hospital have developed a new computational approach to extract molecular interactions from three-dimensional structures. The tool, called MMDBind, was used to elucidate a total of 64,956 new pairwise interactions that were added to the Biomolecular Interaction Network Database (BIND).
The new interactions are the first set of 3D data to be included in BIND, and the work “represents our efforts to completely convert all biologically relevant interaction information from the PDB structure database into BIND format,” said Christopher Hogue, a researcher at the Institute who helped develop the tool.
Until now, BIND has served as a repository for interaction data from published papers in the scientific literature. MMDBind is the first automated tool created to import large numbers of molecular interactions directly into BIND from structure databases. Because three-dimensional crystal structures of molecular complexes can provide detailed information about which amino acids or nucleic acids bind to each other, structural data represents an excellent source of interaction data, said Hogue.
MMDBind draws from the MMDB database, an alternative form of the PDB available through the NCBI Entrez system. Using the atomic coordinate data in MMDB records, MMDBind retrieves selected MMDB records, analyzes the possibiliy of interactions occurring within each record, and then generates the appropriate BIND interaction records.
“Crystallographic interactions are unique and no other approaches can give the same detailed atomic-resolution information,” said Hogue. The interaction information obtained through MMDBind would not have been available through any other technique, he added.
Hogue said MMDBind also removes false interaction information due to crystal-packing artifacts, “so what is left is an incredibly high-quality data set that we will be working with to make the ‘reference’ standard records for BIND.” This reference, called RefBIND, will contain 3D structures annotated with MMDBind, and will interlink with the NCBI RefSeq database.
While the new interaction data is freely available to all users through the BIND database (bind.ca and ftp.bind.ca/DB/MMDBind), the software, which Hogue and colleagues describe in the current issue of Biopolymers, was not intended for release outside of the project. However, said Hogue, “we are happy to field inquiries about the technology or anticipated uses elsewhere.”
The BIND project just received new funding, Hogue noted, and Blueprint Worldwide, the nonprofit organization set up to support the resource, is now hiring additional support staff.