[Chimera-users] Match -> Align used with a pair of homodimers

[Elaine Meng]

Hi Eric,
A couple of us independently tried the process and did not encounter  
the problem.  Using default matchmaker and match->align parameters,  
the two alignments from match->align had 23% and 21% ID.  However, I  
had a theory of where you might have gone astray.  Here are the steps  
of the process:

(1) generate 1nox dimer as a single model.  Note this is much easier  
in newer versions of Chimera (1.3+):  after creating the dimer using  
BIOMT, you can then use the "combine" command or the "copy/combine"  
action in the Model Panel to merge the two monomer models into one  
dimer model with chains A and B.  No hand-editing!

(2) have 1nox dimer and 1ds7 open in Chimera, use Matchmaker with  
default settings.  This gives a sequence alignment of 1ds7 chain B  
and 1nox-dimer chain A with ~26% ID, as you said, and a pretty good- 
looking superposition: final iteration 101 atom pairs, 1.026  
angstroms RMSD.

(3) in Match->Align, you would choose 1ds7 chain B and 1nox-dimer  
chain A as one pair, Apply to get sequence alignment with 23% ID  
(default parameters in Match->Align).  Choosing 1ds7 chain A and 1nox- 
dimer chain B as another pair, clicking Apply gives another sequence  
alignment with 21% ID.

My theory is that maybe you chose A and A as one pair, B and B as  
another pair whereas the superposition really has each A chain on top  
of a B chain.

I hope this helps,
Elaine
-----
Elaine C. Meng, Ph.D.                          meng at cgl.ucsf.edu
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco
                       http://www.cgl.ucsf.edu/home/meng/index.html




On Feb 23, 2009, at 4:41 PM, E. Merkley wrote:

> Hello chimera friends:
>
> I am trying to get a structure-based sequence alignment for a pair of
> homologous proteins that are homodimers.  If I proceed as described  
> in the
> tutorial and in the 2006 BMC Bioinformatics paper, by first using
> Matchmaker, then using Match -> align, the Match -> Align fails to  
> produce
> a reasonable alignment.  The sequence identity from the Matchmaker  
> output
> is 26.5%, but only 1.0 % from the Match -> Align step. If I delete the
> second monomer from each protein, Match -> Align works quite well.
> However, it seems like this alignment won't take into account any
> differences in the tertiary structure between the two proteins.   
> That is,
> I think I want the global alignment of the whole dimer for the  
> structural
> alignment, since the active sites is are at the interface.  Any
> suggestions?  I'm using version 1.2540, and my two proteins are PDB  
> codes
> 1ds7 and 1nox (1nox dimer built from BIOMT matrix in Chimera and
> hand-edited to be 1 model with A and B chains).
>
> Thanks yet again,
> Eric
>