The meaning of alignment: lessons from structural diversity

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-

• Type: Journal
• Year: 2008
• Where: BMCBI
• Authors: Walter Pirovano, K. Anton Feenstra, Jaap Heringa
• Keywords: BMCBI 2008, Proteins, Structural, Structural Alignment