Carrillo and Lipman boundary: Projection of the MSA into series of pairwise alignments Assumption: It is not necessary to compute all the combinations Every pairwise alignment defines a set of spatial positions within which the optimal MSA is suposed to be (heuristic) MSA procedure: Calculate all pairwise alignments and associated distances Use the distances to build a trial phylogenetic tree Calculate pair weights based on the tree (divergence among sequences) Produce a heuristic MSA based on the tree From alignments and the heuristic MSA, determine the relevant positions Perform the optimal alignment (SP-score) within the relevant space