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When two proteins' distance matrices share the same or similar features in approximately the same positions, they can be said to have similar folds with similar-length loops connecting their secondary structure elements. DALI's actual alignment process requires a similarity search after the two proteins' distance matrices are built; this is normally conducted via a series of overlapping submatrices of size 6x6. Submatrix matches are then reassembled into a final alignment via a standard score-maximization algorithm — the original version of DALI used a [[Monte Carlo method|Monte Carlo]] simulation to maximize a structural similarity score that is a function of the distances between putative corresponding atoms. In particular, more distant atoms within corresponding features are exponentially downweighted to reduce the effects of noise introduced by loop mobility, helix torsions, and other minor structural variations.<ref name="Mount" /> Because DALI relies on an all-to-all distance matrix, it can account for the possibility that structurally aligned features might appear in different orders within the two sequences being compared.
The DALI method has also been used to construct a database known as [[Families of structurally similar proteins|FSSP]] (Fold classification based on Structure-Structure alignment of Proteins, or Families of Structurally Similar Proteins) in which all known protein structures are aligned with each other to determine their structural neighbors and fold classification. There is
===Combinatorial extension===
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