Introduction to Bioinformatics

Multiple sequence alignment

'One amino acid sequence plays coy; a pair of homologous sequences whisper; many aligned sequences shout out loud.' In nature, even a single sequence contains all the information necessary to dictate the fold of the protein. How does a multiple sequence alignment make the information more intelligible to us? Alignment tables expose patterns of amino acid conservation, from which distant relationships may be more reliably detected. Structure prediction tools also give more reliable results when based on multiple sequence alignments than on single sequences.

Visual examination of multiple sequence alignment tables is one of the most profitable activities that a molecular biologist can undertake away from the lab bench. Don't even THINK about not displaying them with different colours for amino acids of different physicochemical type. A reasonable colour scheme (not the only one) is:

Colour

Residue type

Amino acids

Yellow

Small nonpolar

Gly, Ala, Ser, Thr

Green

Hydrophobic

Cys, Val, Ile, Leu, Pro, Phe, Tyr, Met, Trp

Magenta

Polar

Asn, Gln, His

Red

Negatively charged

Asp, Glu

Blue

Postively charged

Lys, Arg

To be informative a multiple alignment should contain a distribution of closely- and distantly-related sequences. If all the sequences are very closely related, the information they contain is largely redundant, and few inferences can be drawn. If all the sequences are very distantly related, it will be difficult to construct an accurate alignment (unless all the structures are available), and in such cases the quality of the results, and the inferences they might suggest,...

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