From Protein Structure to Function with Bioinformatics.pdf

2 Fold Recognition 29It has long been clear that similar protein sequences fold to similar structures.Thus, given a novel protein sequence whose structure we require, henceforthknown as the ‘query’, we simply have to check if any other similar sequence witha known structure has already been solved. If the sequences are highly similar thenthis detection process is quite straightforward using simple alignment techniques.Using a simple measure of the similarity of amino acid types, such as the BLOSUMscoring matrix, coupled with a dynamic programming algorithm such as Smith-Waterman, one can rapidly and optimally (according to the scoring function) aligntwo sequences.Given an alignment between a sequence and a known structure, henceforthknown as the ‘template’, one can then build a crude model by simply copying thecorresponding three-dimensional coordinates of the template and re-labelling theamino acids in accordance with the equivalent residues from the alignment (Fig. 2.1).The model can be further refined using a slew of techniques described in the homologyFig. 2.1 Cartoon representation of simple model building by query-template alignment. Thesequence of the known structure (‘Known sequence’) is shown aligned to the query sequence.Dashes represent insertions and deletions. Red letters indicate residue substitutions. Residue typeare coloured according to biophysical properties. Thin wavy lines connect equivalent positions inthe query and template