An intuitive and interactive tool to understand the structure of important biological macromolecules is now available for the readers of the Journal of Inherited Metabolic Disease (JIMD), the leading international journal covering all aspects of inborn errors of metabolism. Called iSee (for Interactive Structural Enhanced Experience), this molecular graphics tool will allow the readers to interactively fly over, zoom into and dive through 3D visualisations in atomic detail.

Recent advances in structural biology are helping other biomedical fields to make significant progresses on several fronts. Understanding the three-dimensional shape of a protein is key to gaining knowledge about the effects of a genetic mutation, and designing drugs to inhibit the action of a disease-associated protein.

In the past scientists have had to use complicated software to view the structures in detail, making it hard for scientists who do not work in this area such as geneticists, pharmaceutical chemists and clinicians to gain access and benefit from this wealth of data.

“This is really a paradigm shift in the way that structural information is shared: our readers can now easily access mutations mapped on available structures of different proteins and enzymes.” said Prof. Johannes Zschocke, editor-in-chief of JIMD and Council Member of the Society for the Study of Inborn Errors of Metabolism (SSIEM), who has been championing the introduction of iSee to the SSIEM community.

This effort has been co-developed with Prof. Udo Oppermann and Dr. Wyatt Yue from the Structural Genomics Consortium (SGC), a public-private partnership with labs at the University of Oxford (UK), the University of Toronto (Canada) and the Karolinska Institutet (Sweden), dedicated to unveiling structures of human proteins of medical relevance which could be targets for new drugs and making them publicly available without any restriction on use.

The first JIMD interactive article presents the structural basis of fumarate hydratase (FH) deficiency, an autosomal recessive metabolic disorder with severe encephalopathy, seizures and poor neurological outcome. The crystal structure of human FH shows that mutations can be mapped and grouped into two distinct classes affecting either structural integrity of the core enzyme architecture, or localised around the enzyme active site.

The reader can access each of the 55 mutations mapped on the structure of FH with a ‘single click and rotate’ and analyse at will – the only requirement is the installation of a free web browser plugin. Instructions on how to do so are presented to the reader when the interactive article is accessed for the first time in a web browser.

iSee has been developed in a collaboration between the SGC and MolSoft LLC and forms a key part of the SGC’s ‘open access’ science philosophy to make its data freely available to all in a manner which maximises the accessibility and understanding for researchers in all fields. “iSee provides a unique way for us to make our data available and accessible to those who will really benefit from it,’ says Dr Brian Marsden from the SGC, who coordinated the development of iSee, together with Dr. Wen Hwa Lee (SGC) and Prof. Ruben Abagyan and his team at MolSoft.

The ground-breaking technology underpinning iSee, known as activeICM, allows any PC or Mac user to run the iSee viewer in web browsers such as Internet Explorer and Firefox (upon installing a plug-in), or to download a standalone viewer for off-line reading.

The first interactive article and editorials accompanying the release of this new, exciting tool can be found in the June issue of JIMD.

Sources: JIMD and the SGC

• Read the JIMD Editorial: Protein structure reports in JIMD - an important enhancement of journal scope.
• Read about the introduction of iSee in JIMD: Interactive JIMD articles using the iSee concept: turning a new page on structural biology data.
• Read the first JIMD enhanced interactive article: Structural basis of fumarate hydratase deficiency. (link to the enhanced article can be found at the end of the abstract)