COBALT: constraint-based alignment tool for multiple protein sequences

Motivation: A tool that simultaneously aligns multiple protein sequences, automatically utilizes information about protein domains, and has a good compromise between speed and accuracy will have practical advantages over current tools. Results: We describe COBALT, a constraint based alignment tool that implements a general framework for multiple alignment of protein sequences. COBALT finds a collection of pairwise constraints derived from database searches, sequence similarity and user input, combines these pairwise constraints, and then incorporates them into a progressive multiple alignment. We show that using constraints derived from the conserved domain database (CDD) and PROSITE protein-motif database improves COBALT's alignment quality. We also show that COBALT has reasonable runtime performance and alignment accuracy comparable to or exceeding that of other tools for a broad range of problems.