Macromolecular Modeling Blog ™

PLoS ONE launched a new collection titled “Structural Biology and Human Health: Medically Relevant Proteins from the SGC” which makes use of three dimensional molecular animation technology.

The SGC (a public-private partnership created to place 3D structures of proteins of medical relevance into the public domain) have been able to take the original research articles published in the Collection and create ‘enhanced’ versions of them. As a result each of the research articles is now also available as an ‘interactive’ version, incorporating user manipulable, three-dimensional molecular structures.

Readers of these enhanced articles first need to download a plug-in for their browser but are then able to click on hyperlinked text within the article to ‘fly’ to the relevant position within the molecule, and to interact with it at will (by zooming, rotating, animating, and exploring). The seamless integration of interactive 3D structures into the actual text of the article provides considerable new functionality for readers, and it is hoped it will lead to new insights and discoveries.

This technology is simmilar to the Proteopedia ongoing project which enables the annotation of structural data with online animation using the wiki and Jmol frameworks.

It seems that the prevalence of both methods would only go as far as the authors of newly published papers would invest time to create these beatiful, educating animations.

Although numerous structures of peptide bound MHC-II molecules were solved, no one knows how does the peptide free MHC look like. Painter et al. elegantly use molecular dynamics to model the conformational changes upon peptide removal. Most interestingly a helix from the peptide binding domain adopts the binding mode of the antigen peptide. They successfully validate their model using antibodies and superantigens, predicted to differentially bind peptide-bound/free molecules according to their model. We take the validation one step further and propose mutations based on Painter’s model that would stabilize the free MHC. Will it work? Who will pick up the gauntlet?

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