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We present a novel algorithm named FAST for aligning protein three-dimensional structures. FAST uses a directionality-based scoring scheme to compare the intra-molecular residueresidue relationships in two structures. It employs an elimination heuristic to promote sparseness in the residue-pair graph and facilitate the detection of the global optimum. In order to test the overall accuracy of FAST, we determined its sensitivity and specificity with the SCOP classification (version 1.61) as thedoi:10.1002/prot.20331 pmid:15609341 fatcat:lod7v3rlsjbo7aalpcxkd6mh4e