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This article is part of the supplement: Proceedings of the European Conference on Computational Biology (ECCB) 2008 Workshop: Annotations, interpretation and management of mutations (AIMM)

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Using structural bioinformatics to investigate the impact of non synonymous SNPs and disease mutations: scope and limitations

Joke Reumers, Joost Schymkowitz and Fréderic Rousseau*

Author Affiliations

Switch Laboratory, VIB, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium

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BMC Bioinformatics 2009, 10(Suppl 8):S9  doi:10.1186/1471-2105-10-S8-S9

Published: 27 August 2009



Linking structural effects of mutations to functional outcomes is a major issue in structural bioinformatics, and many tools and studies have shown that specific structural properties such as stability and residue burial can be used to distinguish neutral variations and disease associated mutations.


We have investigated 39 structural properties on a set of SNPs and disease mutations from the Uniprot Knowledge Base that could be mapped on high quality crystal structures and show that none of these properties can be used as a sole classification criterion to separate the two data sets. Furthermore, we have reviewed the annotation process from mutation to result and identified the liabilities in each step.


Although excellent annotation results of various research groups underline the great potential of using structural bioinformatics to investigate the mechanisms underlying disease, the interpretation of such annotations cannot always be extrapolated to proteome wide variation studies. Difficulties for large-scale studies can be found both on the technical level, i.e. the scarcity of data and the incompleteness of the structural tool suites, and on the conceptual level, i.e. the correct interpretation of the results in a cellular context.