1. 11 Ch6 multiple sequence alignment methods 1 Biologists produce high quality multiple sequence alignment by hand using knowledge of protein sequence evolution. Automatic multiple sequence alignment? -in probabilistic modeling, scoring function is primary concern, not the alignment algorithm

2. 2 6.1 What a multiple alignment means

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4. 4 In principle, there is always an unambiguously correct evolutionary alignment even if the structures diverge In practice, an evolutionarily correct alignment can be more difficult to infer than structural alignment Our ability to define a single ‘correct’ alignment will vary with the relatedness of the sequences being aligned Usually, a small subset of key residues will be identifiable which can be aligned unambiguously almost regardless of the sequence divergence We should focus on the subset of columns corresponding to key residues and core structural elements that can be aligned with confidence

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9. 9 6.3 Multidimensional dynamic programming

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11. 11 MSA (Carrillo & Lipman)

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13. 13 6.4 Progressive alignment methods

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15. 15 Profile alignment

16. 16 CLUSTALW

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18. 18 Iterative refinement methods

19. 19 6.5 Multiple alignment by profile HMM

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