DALI and the persistence of protein shape

DALI is a popular resource for comparing protein structures. The software is based on distance-matrix alignment. The associated web server provides tools to navigate, integrate and organize some data pushed out by genomics and structural genomics. The server has been running continuously for the past 25 years. Structural biologists routinely use DALI to compare a new structure against previously known protein structures. If significant similarities are discovered, it may indicate a distant homology, that is, that the structures are of shared origin. This may be significant in determining the molecular mechanisms, as these may remain very similar from a distant predecessor to the present day, for example, from the last common ancestor of humans and bacteria. Meta-analysis of independent reference-based evaluations of alignment accuracy and fold discrimination shows DALI at top rank in six out of 12 studies. The web server and standalone software are available from .