Abstract
BackgroundProtein structural alignment provides a fundamental basis for deriving principles of functional and evolutionary relationships. It is routinely used for structural classification and functional characterization of proteins and for the construction of sequence alignment benchmarks. However, the available techniques do not fully consider the implications of protein structural diversity and typically generate a single alignment between sequences.ResultsWe have taken alternative protein crystal structures and generated simulation snapshots to explicitly investigate the impact of structural changes on the alignments. We show that structural diversity has a significant effect on structural alignment. Moreover, we observe alignment inconsistencies even for modest spatial divergence, implying that the biological interpretation of alignments is less straightforward than commonly assumed. A salient example is the GroES 'mobile loop' where sub-Ångstrom variations give rise to contradictory sequence alignments.ConclusionA comprehensive treatment of ambiguous alignment regions is crucial for further development of structural alignment applications and for the representation of alignments in general. For this purpose we have developed an on-line database containing our data and new ways of visualizing alignment inconsistencies, which can be found at .
Highlights
Protein structural alignment provides a fundamental basis for deriving principles of functional and evolutionary relationships
Structural alignment is the method of choice for reliable homology assessment and derived features like functional classification and phylogeny
It is clear that the structural variation between crystal structures is much smaller than that of the simulation snapshots
Summary
Protein structural alignment provides a fundamental basis for deriving principles of functional and evolutionary relationships It is routinely used for structural classification and functional characterization of proteins and for the construction of sequence alignment benchmarks. Structural alignment is the method of choice for reliable homology assessment and derived features like functional classification and phylogeny This importance is reflected in the number of tools available for structural alignment, such as DALI [1], SSAP [2], STRUCTAL [3], MAMMOTH [4], CE [5] and COMPARER [6] (for recent reviews on the topic, see Kolodny et al [7] and Mayr et al [8]).
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