Stories from the grid: the cone snail and the search for powerful new anaesthetics

ORIGINAL: EuropeanGrid  WE-NMR

Episode 1: a short film about how a component of the venom used by the marine cone snail to hunt for food can help to create new painkillers. Researchers are using grid computing to digitally modify molecules found in the venom. The grid allows them to run a lot of trial and error tests extremely quickly to look for the right molecular shape that will be the perfect fit for the pain receptors in humans.

'Stories from the Grid' is a series of three short films which explore how researchers from different scientific disciplines are using cutting edge grid computing technology to advance their work.

The WeNMR web Portals for Structural Biology
Submitted by Chris Spronk on Wed, 2011-07-20 12:03

The web portals developed within WeNMR are among the most important elements of the project, as these form the points of entry for the end users.

The ultimate goal is to offer to users registered with the eNMR/WeNMR Virtual Organization (VO) complete online protocols for processing NMR data, including all the steps depicted in Figure 1.

Fig. 1 NMR data processing from signal to 3D structure  

After acquisition of the primary NMR data, these are Fourier transformed to obtain spectra in which the individual frequency contributions or resonances of spin systems, and their relations, are revealed.

The resonances subsequently have to be assigned to individual atoms. If sufficient resonances have been assigned, restraints can be inferred from the data, pertaining to distances between atoms, dihedral angles, domain orientations, etc. When an adequate number of restraints is available, these can be used to calculate a set of three-dimensional structures optimally satisfying these restraints.

The resulting structures represent the structure of the protein in solution, which is validated against the available experimental data. Although the process is here depicted linearly, intermediate stages may involve iterative cycles of refinement.

In addition, each of these steps, and every program involved has value by itself as web based service. For this reason, a piece-wise implementation has been adopted and programs that are ported to the Grid are simultaneously being made available as a web portal. Currently, 12 portals are operational and can be accessed through http://www.wenmr.eu/wenmr/nmr-services. These provide access, among other services, to

• HADDOCK for the prediction of biomolecular complexes
• XPLOR-NIH
• CYANA and CS-ROSETTA for calculating structures from NMR data
• AMBER for structure refinement and molecular dynamics (MD) simulations
• CcpNmr for data conversion
• MARS for backbone assignment
• TALOS+ for torsion angle prediction
• MDDNMR for NUS spectral processing

Next to these available portals, several new ones are in development for various NMR applications, including the UNIO program that provides computational routines for each individual step depicted in Figure 1.