Structural Differences between Proteins with Similar Sequences

Similarity between protein sequences is usually predictive of similarity in structures. However, in some rare cases protein domains with significant sequence similarity adopt different structures. Here, we carry out a survey of protein domain pairs with high sequence similarity (measured by HHsearch probability) and low structural similarity (measured by Dali Z-score), aiming to identify the reasons for this discordance. Besides methodological problems with either sequences or structures of domains, we find and describe novel examples of homologs with structural changes.