Structure and function analysis of flexible alignment regions in proteins
© Pirovano et al; licensee BioMed Central Ltd. 2009
Published: 19 October 2009
Protein structural alignment plays a key role in defining gold standards for a variety of bioinformatics applications. These include homology assessment, phylogenetic tree construction and multiple sequence alignment evaluation. Our recent findings  however showed that superposition methods are rather sensitive to structural variation. To sidestep the problem of alignment variability, golden standards are often derived from the more conserved and 'trusted' regions. It therefore remains unclear which structural elements characterize alignment variability and what functional information these discarded flexible regions entail.
Our results imply that the current 'gold' standard status of structural alignment should be considered 'silver'. Particularly our observation that helices are associated with flexible alignment regions is at odds with currently used alignment strategies. Moreover, given that functional importance is spread evenly between stably and flexibly aligned regions, we conclude that flexible regions cannot be excluded from analysis of functionality in proteins. In order to explore new strategies for homology detection, phylogeny and alignment we propose that, as a first step, more golden standards be developed that can more comprehensively represent the structural, functional and evolutionary signals.
Financial support for this project was provided by the Netherlands Bioinformatics Centre, BioRange Bioinformatics research programme SP 3.2.2.
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