Multiple Sequence Alignment Overview of Clustal W Procedure

Multiple Sequence Alignment

Overview of Clustal. W Procedure Hbb_Human Hbb_Horse Hba_Human Hba_Horse Myg_Whale 1 2 3 4 5 . 17. 59. 77 Clustal. W. 60. 59. 77 . 13. 75 Hbb_Human . 75 - 2 3 Quick pairwise alignment: calculate distance matrix 4 Hbb_Horse Hba_Human Neighbor-joining tree (guide tree) 1 Hba_Horse Myg_Whale alpha-helices 1 2 3 4 5 PEEKSAVTALWGKVN--VDEVGG GEEKAAVLALWDKVN--EEEVGG PADKTNVKAAWGKVGAHAGEYGA AADKTNVKAAWSKVGGHAGEYGA EHEWQLVLHVWAKVEADVAGHGQ 2 1 3 4 Progressive alignment following guide tree

Clustal. W- Pairwise Alignments • First perform all possible pairwise alignments between each pair of sequences. There are (n-1)+(n-2). . . (n-n+1) possibilities. • Calculate the ‘distance’ between each pair of sequences based on these isolated pairwise alignments. • Generate a distance matrix.

Path graph for aligning two sequences

Possible alignment 1 Scoring Scheme: • Match: +1 • Mismatch: 0 • Indel: -1 1 0 1 Score for this path= 2 0 -1

Alignment using this path 1 1 GATTCGAATTC 0 1 0 -1

Optimal Alignment 1 Alignment using this path 1 1 GA-TTC GAATTC -1 1 1 Alignment score: 4 1

Optimal Alignment 2 ? Alignment score: 4

Optimal Alignment 2 1 Alignment using this path -1 G-ATTC GAATTC 1 1 1 Alignment score: 4 1

Clustal. W- Guide Tree • Generate a Neighbor-Joining ‘guide tree’ from these pairwise distances. • This guide tree gives the order in which the progressive alignment will be carried out.