A metadata-driven approach to data repository design.

The design and use of a metadata-driven data repository for research data management is described. Metadata is collected automatically during the submission process whenever possible and is registered with DataCite in accordance with their current metadata schema, in exchange for a persistent digital object identifier. Two examples of data preview are illustrated, including the demonstration of a method for integration with commercial software that confers rich domain-specific data analytics without introducing customisation into the repository itself.

Standards-based curation of a decade-old digital repository dataset of molecular information.

BACKGROUND: The desirable curation of 158,122 molecular geometries derived from the NCI set of reference molecules together with associated properties computed using the MOPAC semi-empirical quantum mechanical method and originally deposited in 2005 into the Cambridge DSpace repository as a data collection is reported. RESULTS: The procedures involved in the curation included annotation of the original data using new MOPAC methods, updating the syntax of the CML documents used to express the data to ensure schema conformance and adding new metadata describing the entries together with a XML schema transformation to map the metadata schema to that used by the DataCite organisation. We have adopted a granularity model in which a DataCite persistent identifier (DOI) is created for each individual molecule to enable data discovery and data metrics at this level using DataCite tools. CONCLUSIONS: We recommend that the future research data management (RDM) of the scientific and chemical data components associated with journal articles (the "supporting information") should be conducted in a manner that facilitates automatic periodic curation. Graphical abstractStandards and metadata-based curation of a decade-old digital repository dataset of molecular information.

Insights from Fragment Hit Binding Assays by Molecular Simulations.

Novel bioactive molecules can be rationally designed by growing and linking small fragments. Because fragments are fast and promiscuous, it is common to have contradictory hit results between different experimental screening techniques. Here, we simultaneously determine fragment binding poses, affinities, and kinetics on a focused library of 42 fragments against the serine protease factor Xa using multimillisecond molecular dynamics simulations. We predict experimental poses of 12 over 15 S1 crystal structures, and affinities are recovered for 4 out of 6. A kinetic map of protein cavities is computed in terms of on- and off-rates as well as insights into secondary ligand poses. The results suggest that the approach can be useful to recapitulate discordant fragment screening data.

Standards-based metadata procedures for retrieving data for display or mining utilizing persistent (data-DOI) identifiers.

BACKGROUND: We describe three different procedures based on metadata standards for enabling automated retrieval of scientific data from digital repositories utilising the persistent identifier of the dataset with optional specification of the attributes of the data document such as filename or media type. RESULTS: The procedures are demonstrated using the JSmol molecular visualizer as a component of a web page and Avogadro as a stand-alone modelling program. We compare our methods for automated retrieval of data from a standards-compliant data repository with those currently in operation for a selection of existing molecular databases and repositories. CONCLUSIONS: Our methods illustrate the importance of adopting a standards-based approach of using metadata declarations to increase access to and discoverability of repository-based data. Graphical abstract.

Digital data repositories in chemistry and their integration with journals and electronic notebooks.

We discuss the concept of recasting the data-rich scientific journal article into two components, a narrative and separate data components, each of which is assigned a persistent digital object identifier. Doing so allows each of these components to exist in an environment optimized for purpose. We make use of a poorly-known feature of the handle system for assigning persistent identifiers that allows an individual data file from a larger file set to be retrieved according to its file name or its MIME type. The data objects allow facile visualization and retrieval for reuse of the data and facilitates other operations such as data mining. Examples from five recently published articles illustrate these concepts.

High-throughput molecular dynamics: the powerful new tool for drug discovery.

Molecular dynamics simulations are capable of resolving molecular recognition processes with chemical accuracy, but their practical application is popularly considered limited to the timescale accessible to a single simulation, which is far below biological timescales. In this perspective article, we propose that the true limiting factor for molecular dynamics is rather the high hardware and electrical power costs, which constrain not only the length of runs but also the number that can be performed concurrently. As a result of innovation in accelerator processors and high-throughput protocols, the cost of molecular dynamics sampling has been dramatically reduced and we argue that molecular dynamics simulation is now placed to become a key technology for in silico drug discovery in terms of binding pathways, poses, kinetics and affinities.