Structure-based PAM scores: was (And now for something completely diffe

goldman at mbcl.rutgers.edu goldman at mbcl.rutgers.edu
Wed Jul 1 14:15:43 EST 1992

In article <1992Jun23.171414.4745 at jhunix.hcf.jhu.edu>, johnk at jhunix.hcf.jhu.edu (John J Kuszewski) writes:
> I remember a few posts (before the current thread began) about how to 
> calculate the "cost" of an insertion during sequence comparisons.  In
> general, the cost is of the form a + bx, where a is a constant cost
> for making any insertion, b is the cost per inserted residue, and x is
> the number of residues inserted.
> This doesn't seem to make a whole lot of sense.  An insertion at a site
> on the surface of a protein should be a lot less expensive to make than
> at an interior site.  
> Are there programs that, given a particular structure, will find sequence 
> relatives (ala David Eisenberg), using a cost function that varies with the
> three-dimensional position of the insertion?  Since residue exposure is 
> one of Eisenberg's environment criteria, this should be straightforward to 
> implement.
Well, forgive me if I have this upside down, but let's look at the false
positive rate.  In the limit, you have a sequence that is *completely
unrelated* to the sequence/structure you are comparing it with.  The region
you are scanning is inside, but you are moving it past the outside region
of the test structure.  Consequently, your gap weight & extension weight
(or other parameters, however defined) go low.  Shall we say, for argument's
sake, that they go to zero?  Then you'll get a perfect match between regions
(by inserting lots of *long* gaps) that are completely unrelated.

Plus (go look at a structure) outside is a *very* temporary thing on a protein
surface.  For instance: on a beta-strand on the edge of the protein, every
second amino-acid could be an "inside" amino acid.  Or in an alpha-helix
that's mostly buried, ~1/4 amino-acids will be outside.

> It might even make for better alignments.
All in all, I don't think so.

               Adrian Goldman

Goldman at MBCL.Rutgers.Edu

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