Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/23261
Title: Traditional biomolecular structure determination by NMR spectroscopy allows for major errors
Authors: Nabuurs, S. B.
Spronk, C. A.
Vuister, Geerten W.
Vriend, G.
First Published: 3-Feb-2006
Publisher: Public Library of Science
Citation: PLoS Computational Biology, 2006, 2 (2), e9
Abstract: 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.
DOI Link: 10.1371/journal.pcbi.0020009
eISSN: 1553-7358
Links: http://hdl.handle.net/2381/23261
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2006 Nabuurs et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Biochemistry

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