A worldwide e-Infrastructure for NMR and structural biology

Traditional Biomolecular Structure Determination by NMR Spectroscopy Allows for Major Errors

Typearticle
Date PLoS Computational Biology, 2(2), e9.
AuthorsSander B. Nabuurs, Chris A. E. M. Spronk, Geerten W. Vuister, Gert Vriend
Year2005

One of the major goals of structural genomics projects is to determine the three-dimensional structure of representative members of as many different fold families as possible. Comparative modeling is expected to fill the remaining gaps by providing structural models of homologs of the experimentally determined proteins. However, for such an approach to be successful it is essential that the quality of the experimentally determined structures is adequate. In an attempt to build a homology model for the protein dynein light chain 2A (DLC2A) we found two potential templates, both experimentally determined nuclear magnetic resonance (NMR) structures originating from structural genomics efforts. Despite their high sequence identity (96%), the folds of the two structures are markedly different. This urged us to perform in-depth analyses of both structure ensembles and the deposited experimental data, the results of which clearly identify one of the two models as largely incorrect. Next, we analyzed the quality of a large set of recent NMR-derived structure ensembles originating from both structural genomics projects and individual structure determination groups. Unfortunately, a visual inspection of structures exhibiting lower quality scores than DLC2A reveals that the seriously flawed DLC2A structure is not an isolated incident. Overall, our results illustrate that the quality of NMR structures cannot be reliably evaluated using only traditional experimental input data and overall quality indicators as a reference and clearly demonstrate the urgent need for a tight integration of more sophisticated structure validation tools in NMR structure determination projects. In contrast to common methodologies where structures are typically evaluated as a whole, such tools should preferentially operate on a per-residue basis.

Contacts

Chris Spronk

Cite WeNMR

 
Usage of the WeNMR portals should be acknowledged in any publication:
 
"The WeNMR project (European FP7 e-Infrastructure grant, contract no. 261572www.wenmr.eu), supported by the European Grid Initiative (EGI) through the national GRID Initiatives of Belgium, France, Italy, Germany, the Netherlands, Poland, Portugal, Spain, UK, South Africa, Malaysia, Taiwan, the Latin America GRID infrastructure via the Gisela project, the International Desktop Grid Federation (IDGF) with its volunteers and the US Open Science Grid (OSG) are acknowledged for the use of web portals, computing and storage facilities. "
 
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.

EGI-approved

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