The meaning of alignment: lessons from structural diversity Export

@article{pirovano_08_meaning, abstract = {BACKGROUND: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.RESULTS: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-Angstrom variations give rise to contradictory sequence alignments.CONCLUSIONS: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 www.ibi.vu.nl/databases/stralivari.}, author = {Pirovano, Walter and Feenstra, Anton K. and Heringa, Jaap}, citeulike-article-id = {3822493}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1471-2105-9-556}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19105835}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19105835}, doi = {10.1186/1471-2105-9-556}, issn = {1471-2105}, journal = {BMC Bioinformatics}, keywords = {alignment, evolution, structure, validation}, number = {1}, posted-at = {2008-12-27 18:35:07}, priority = {2}, title = {The meaning of alignment: lessons from structural diversity}, url = {http://dx.doi.org/10.1186/1471-2105-9-556}, volume = {9}, year = {2008} }

TY - JOUR ID - pirovano_08_meaning L3 - citeulike-article-id:3822493 N2 - BACKGROUND: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.RESULTS: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-Angstrom variations give rise to contradictory sequence alignments.CONCLUSIONS: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 www.ibi.vu.nl/databases/stralivari. IS - 1 JF - BMC Bioinformatics SN - 1471-2105 TI - The meaning of alignment: lessons from structural diversity VL - 9 KW - alignment KW - evolution KW - structure KW - validation AU - Pirovano, Walter AU - Feenstra, Anton AU - Heringa, Jaap PY - 2008/// UR - http://dx.doi.org/10.1186/1471-2105-9-556 ER -