SEQUENCE_COMPARISON: wrong calculation for variability

["Timothy A. Springer Ph.D." <>]

I like the sequence comparison functions in Modeller.  I would like to
calculate sequence conservation or variabilty as a function of position.
One of the proteins I work with contains a conserved domain, and I would
like to plot this.  Unfortunately, variability as a function of alignment
position is not calculated in a meaningful way.  It does calculate what it
says it calculates, but the result is not helpful at all - it is the RMS
deviation of all residue - residue scores.  I have plotted this, and it
shows little relationship to highly conserved areas.  It picks up positions
of identity fine, but that is about it.

Could you please implement a calculation of sequence conservation.  I
suggest the total of the similarity scores.  You could divide this by the
maximal number of sequence comparisons.  I would not divide by the number
of comparisons at each position, because this may be small for positions
with gaps, and might overestimate conservation in gapped regions.

Also, the documentation says gaps are included in the scoring matrix, but
this is only true for the blosum matrix.

Thanks, Tim Springer


>From the manual:
SEQUENCE_COMPARISON -- compare sequences in alignment
Description:
The family variability as a function of alignment position is calculated as
the RMS deviation of all residue - residue scores at a given
       position, but only for those alignment positions that have at most
MAX_GAPS_MATCH  gaps. The variability is written to file
       VARIABILITY_FILE , as is the number of pairwise comparisons
contributing to each positional variability.


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*  Timothy A. Springer, Ph.D.                                                 *
*  Latham Family Professor of Pathology                                       *
*  Harvard Medical School            e-mail:   *
*  Center for Blood Research            phone:  617-278-3200                  *
*  200 Longwood Ave.  Room 251          fax:    617-278-3232                  *
*  Boston MA 02115                                                            *
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