The meaning of alignment: lessons from structural diversity

<p>Abstract</p> <p>Background</p> <p>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 th...

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Main Authors: Heringa Jaap, Feenstra K Anton, Pirovano Walter
Format: Article
Language:English
Published: BMC 2008-12-01
Series:BMC Bioinformatics
Online Access:http://www.biomedcentral.com/1471-2105/9/556
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author Heringa Jaap
Feenstra K Anton
Pirovano Walter
author_facet Heringa Jaap
Feenstra K Anton
Pirovano Walter
author_sort Heringa Jaap
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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. However, the available techniques do not fully consider the implications of protein structural diversity and typically generate a single alignment between sequences.</p> <p>Results</p> <p>We 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.</p> <p>Conclusion</p> <p>A 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 <url>http://www.ibi.vu.nl/databases/stralivari</url>.</p>
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spelling doaj.art-73e50050b2314ad5a0d32fe30344f68d2022-12-21T18:11:58ZengBMCBMC Bioinformatics1471-21052008-12-019155610.1186/1471-2105-9-556The meaning of alignment: lessons from structural diversityHeringa JaapFeenstra K AntonPirovano Walter<p>Abstract</p> <p>Background</p> <p>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. However, the available techniques do not fully consider the implications of protein structural diversity and typically generate a single alignment between sequences.</p> <p>Results</p> <p>We 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.</p> <p>Conclusion</p> <p>A 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 <url>http://www.ibi.vu.nl/databases/stralivari</url>.</p>http://www.biomedcentral.com/1471-2105/9/556
spellingShingle Heringa Jaap
Feenstra K Anton
Pirovano Walter
The meaning of alignment: lessons from structural diversity
BMC Bioinformatics
title The meaning of alignment: lessons from structural diversity
title_full The meaning of alignment: lessons from structural diversity
title_fullStr The meaning of alignment: lessons from structural diversity
title_full_unstemmed The meaning of alignment: lessons from structural diversity
title_short The meaning of alignment: lessons from structural diversity
title_sort meaning of alignment lessons from structural diversity
url http://www.biomedcentral.com/1471-2105/9/556
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