A worldwide e-Infrastructure for NMR and structural biology

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Getting started with CS-ROSETTA

Chemical-Shift ROSETTA or CS-ROSETTA is the third program for structure calculations that has been ported to the Grid and made available through the WeNMR web portal. CS-ROSETTA, unlike XPLOR-NIH and CYANA, allows structure determination of proteins, based on chemical shift information alone. It thus bypasses the need for NOE based distance restraints, which usually require considerable time to obtain. Further advantages of using chemical shifts are that these are among the most reliable parameters that can be obtained from NMR spectroscopy and that they can potentially be obtained for larger macromolecules for which NOEs become impractical. On the other hand, direct chemical shift based structure determination is computationally much more expensive than structure calculations using distance restraints.  However, the most time consuming part of a CS-ROSETTA run consists of a large number of independent calculations that can be easily distributed over the Grid.

Structure determination using CS-ROSETTA requires as only input the amino acid sequence and a list of chemical shifts and a number of parameters to control the process that can be changed from the default values. Backbone chemical shifts for 13Ca, 13Cb, 13C’, 1Ha, 1HN, and 15N that are provided by the user, are validated and stored as the target shifts.  These chemical shifts are first used to select a set of protein fragments from a structure database, e.g. the Protein Data Bank (PDB), based on the list of chemical shifts as predicted with SPARTA. Then the regular ROSETTA protocol for Monte Carlo assembly and relaxation is used to reassemble the protein from the fragments. For the resulting models the chemical shifts are again predicted using SPARTA and the deviations between the predicted and target values are used as a pseudo-energy term in the scoring of the models, yielding a ranking based on both overall structural quality as well as on the match with the experimental data.

The computationally most expensive step in the process is the construction of a model using Monte Carlo assembly and relaxation. To obtain a reliable prediction, a set of 10 000 to 50 000 models has to be built, each starting from the same fragment library. Using different seeds for generation of random numbers ensures independence of the results from different runs. For the WeNMR implementation of CS-ROSETTA only the Monte Carlo search is performed on the Grid.

The computational cost involved in chemical shift based structure determination makes CS-ROSETTA a typical example of a program that is beyond the capacity of most local sites. Here, the access to Grid resources through a web-portal, combining computational power and ease of use, clearly demonstrates its added value. 

To use the service, users have to register with a valid Grid certificate to obtain a user name and password that can subsequently be used to sign service requests. The web interface for CS-ROSETTA itself is straightforward and only requires uploading a file containing chemical shifts in TALOS format, and modifying the parameters to control the calculations. When the job has finished, the user receives an e-mail containing a link to the result page that gives an overview of the run, including some statistics and images to assess the overall quality of the results. The user can then select a number of structures to view in more detail or to download, or choose to download the whole set of results as an archive.  


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Cite WeNMR/WestLife

Usage of the WeNMR/WestLife portals should be acknowledged in any publication:
"The FP7 WeNMR (project# 261572), H2020 West-Life (project# 675858) and the EOSC-hub (project# 777536) European e-Infrastructure projects are acknowledged for the use of their web portals, which make use of the EGI infrastructure with the dedicated support of CESNET-MetaCloud, INFN-PADOVA, NCG-INGRID-PT, TW-NCHC, SURFsara and NIKHEF, and the additional support of the national GRID Initiatives of Belgium, France, Italy, Germany, the Netherlands, Poland, Portugal, Spain, UK, Taiwan and the US Open Science Grid."
And the following article describing the WeNMR portals should be cited:
Wassenaar et al. (2012). WeNMR: Structural Biology on the Grid.J. Grid. Comp., 10:743-767.


The WeNMR Virtual Research Community has been the first to be officially recognized by the EGI.

European Union

WeNMR is an e-Infrastructure project funded under the 7th framework of the EU. Contract no. 261572

WestLife, the follow up project of WeNMR is a Virtual Research Environment e-Infrastructure project funded under Horizon 2020. Contract no. 675858