prss3 is used to evaluate the significance of a protein or DNA sequence similarity score by comparing two sequences and calculating optimal similarity scores, and then repeatedly shuffling the second sequence, and calculating optimal similarity scores using the Smith-Waterman algorithm. An extreme value distribution is then fit to the shuffled-sequence scores. The characteristic parameters of the extreme value distribution are then used to estimate the probability that each of the unshuffled sequence scores would be obtained by chance in one sequence, or in a number of sequences equal to the number of shuffles.