Re: MULTIPLE/SINGLE templates for modelling.

[Karsten Suhre <>]

Hi!

  along this line I would like to add the following question to the 
discussion:

 I agree that multiple structural alignments (MSAs) are the best starting 
point for homology modelling. 

  However, how can you pass (sequence-independant) information about the 
quality of the alignment to Modeller? T-COFFEE for example outputs an 
alignment score (CORE index) that gives you the confidence that we can have 
in the alignment (locally - residue by residue). This CORE index is 
independant of the amino acid composition! It may tell you for example that 
two sequences that share much less sequence homology than two others are 
structurally much closer than the two sharing a higher sequence homology. 

At present I don't see an easy way to pass this information on to Modeller, 
except by editing the alignment by hand.

  I would be interested in your comments,

  Kind regards, Karsten Suhre. (IGS-CNRS, Marseille, Fance)


> > I feel the alignment itself should take care of everything. I heard about
> > using multiple templates in such cases. How is this approach followed and
> > how good is it ?

> The alignment is of paramount importance (as you would read if you look
> at the archives of this mailing list). For multiple templates, one must
> take care that multiple sequence alignment artefacts are not introduced.
> Whilst a good MSA will provide the best alignment data for a homology
> model, sometimes there are locally inconsistent residue mappings, sometimes
> within conserved regions of secondary structure, because one or more
> of the proteins has a region of low homology. If these are not filtered
> out, ultimately by a little trial and error, then they can severely reduce
> the model quality.