Drug discovery

Organising, linking and discovering biomolecule structural data

Structural biology is producing unprecedented amounts of data that increase not only in number, but also in size and complexity and that span an ever-wider range of resolutions, including low-resolution data. While there are very good bioinformatics tools for the analysis, validation and comparison of detailed atomic structures, at present there are very few tools available to work with low-resolution data (i.e. volume or shape data).

However, low-resolution data can have very high value and is gaining in importance. In Cryo-electron microscopy (cryoEM) for example, specimens are viewed in their physiological environment, preserving the natural conformations of molecules. This is necessary for example to check what structural changes might be induced by a drug binding to a target. BioMedBridges addresses the need to analyse low-resolution data by developing a web-based service for searching the PDBe and EMDB public archives based on shape (volume data). By comparing the shape of a given biomolecule with the contents of the public archives, the service will enable the identification of known structures that have a similar shape. This will be further enhanced by the integration of software that enables the determination of the shape of various protein conformations sampled in solution in which they experience some kind of mobility, which presents a challenge to shape determination.As a first step, the software underlying the shape-matching service was completed in December 2014; the web-based service is scheduled to be launched in March 2015.

Another web-based service will enable the decomposition of volume data into its components (e.g. various proteins, possibly RNA or DNA etc.), which will support the interpretation of complex volume data in terms of possible and plausible structures of components of that data (e.g. when annotating particles in a tomogram).

Finally, BioMedBridges has provided a new RESTful interface for PiMS, a laboratory information management system for use in protein production laboratories. This interface enables the analysis of PiMS data in light of other datasets, such as protein sequence and structural information, and enables a future vision of tools which track the provenance of published biomedical results to the datasets and samples involved in the research project.

Unlocking small-molecule resources

UniChem supports the integration of high-throughput screening data on small molecules with chemical libraries and chemical resources for drug discovery and optimization. A new search function enables researchers to find not only “same” compounds across different resources, but also “similar” compounds, allowing discovery of a much wider range of results from a larger number of resources, ultimately making a significant contribution towards drug discovery also by industrial users.

Tools and resources