Alignment of sequence to tertiary structure

Remember that the alignments of sequence on to tertiary structure that one gets from fold recognition methods may be inaccurate. In instance where one has identified a remote homologue, then the fold recognition methods can sometimes give a very accurate alignment, though it is still sometimes fruitful to edit the alignment around variable regions (see the Multiple Sequence Alignment for ways of doing this). In other cases, it may be wise to create your own alignment by starting with the alignment from the fold recognition method, and considering the alignment of secondary structures.

There is no generally accepted way for doing this, though one method (ie. mine) involves:

For example, in trying to align the prediction of the glutamyl tRNA reductases (hemA) with one alpha/beta barrel structure (2acs):

[Sec.= known secondary structure from PDB code 2ACS (E = extended, H = alpha helix, G = 3-10 helix, B = beta-bridge); Bur. = known residue exposure for 2ACS (b = buried, h = half-buried, e = exposed); in/out = positioning of residues in the beta-barrel (i = pointing inwards, o = pointing outwards); Res. cons = conservation of residues (totally conserved = UPPER CASE, h = hydrophobic, p = polar, c = charged, a = aromatic, s = small, - = negaitve, + = positive) Pred denotes predicted burial and secondary structure for the glutamyl tRNA reductase family; boxed positions are those with the same known/predicted burial. Shaded positions show a conservation of hydrophobic character in BOTH families of proteins, and positions in inverse text show a conservation of polar character in BOTH families.]

In the construction of this alignment, several things were considered:

By using an initial alignment from one of the fold recognition methods as a guide, the alignment above was created by trying to optimise the match of features described above.

Remember that proteins having similar three-dimensional structures with little or no sequence similarity can differ substantial with respect to the finer details of their structures (i.e. loops, precise orientation of side chains, orientation of secondary structures, etc.). See here for some work I did with Geoff Barton on this subject.

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