Background: We present a complete re-implementation of the segment-based approach to multiple protein alignment that contains a number of improvements compared to the previous version 2.2 of DIALIGN. This previous version is superior to Needleman-Wunsch-based multialignment programs on locally related sequence sets. However, it is often outperformed by these methods on data sets with global but weak similarity at the primary-sequence level. Results: In the present paper, we discuss strengths and weaknesses of DIALIGN in view of the underlying objective function. Based on these results, we propose several heuristics to improve the segment-based alignment approach. For pairwise alignment, we implemented a fragment-chaining algorithm that favours chains of low-scoring local alignments over isolated high-scoring fragments. For multiple alignment, we use an improved greedy procedure that is less sensitive to spurious local sequence similarities. To evaluate our method on globally related p...
Amarendran R. Subramanian, Jan Weyer-Menkhoff, Mic