Gaps and PAMs

goldman at mbcl.rutgers.edu goldman at mbcl.rutgers.edu
Wed Jul 1 14:30:37 EST 1992

In article <eddy.709823869 at beagle>, eddy at boulder.Colorado.EDU (Sean Eddy) writes:
> gonnet at inf.ethz.ch (Gaston Gonnet) writes:

..stuff deleted to save net.bandwidth...

>>I am afraid that you
>>tend to imply that alignment is "black magic" or "art".  I disagree
>>strongly with this view.  We should establish models, compute the
>>parameters for these models, verify/reject the models against reality
>>and move into better models when the old ones become unsuitable to
>>describe reality.  This is the way that science makes progress, not
>>with "subjective measures".  There are hundreds of examples of this
>>methodology in science.
> What "reality" are you going to test, for determining the accuracy
> of your methods for aligning distantly similar sequences? Is there
> a set of sequences with distantly related sequences but similar
> enough 3D structures to permit a confident structure-based alignment?
> I'd love to know of one (seriously).
Actually, there are some examples.  If you believe Farber & Petsko in TIBS,
you could take all the TIM barrel enzymes.  They claim that all of them
are related by divergent evolution.  (I personally don't buy it.) 
Alternatively, take a look at Protein Engineering, vol5, p197-211, 1992.
In it, we (yes, I'm sorry to say, this is a commercial!) discuss a new 
protein fold where four of the five members of the fold were not known to be
related before their structures were solved.  And indeed meaningful structural
alignments can be made (that will have *enormous* insertions in them: some
of these insertions, by the way, in the *interior* of the proteins).

                    Adrian Goldman

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