Equivalent amino acids for similarity searches

Peter Gegenheimer peterg at rnaworld.bio.ukans.edu
Sat Mar 26 21:21:13 EST 1994

In <2mv3ch$ksn at lyra.csx.cam.ac.uk>, smb18 at mole.bio.cam.ac.uk (Simon Brocklehurst (Bioc)) writes:
>Notwithstanding all that has preceeded this thread, it is probably worth
>pointing out that the physico-chemical properties of amino-acids ARE
>of course reflected in the pattern amino acid substitutions that are
>observed in divergently evolved families of proteins.  When this doesn't
>happen, it's often because a particular position a fold doesn't have 
>ANY real preference for a type of residue e.g a lot of surface positions
>fall into this catagory.

As one of the preceding posters, I concur with this advice. What I meant was that
evolution is looking at many properties of an amino acid, not necessarily the ones 
you are familiar with. As an example, one can't always make the simple assumption
that Cys (a small thiol) is replaceable with Ser or Thr (a small alcohol). In fact, 
although one often sees interchanges among Ser, Thr, and Ala, interchanges with Cys 
are not very common. Our experience was that Cys-> Ala or even Val works OK - 
suggesting the greater hydrophobicity of Cys vs Ser/Thr makes an aliphatic sidechain 
preferable. This was for a Cys deduced to be at a subunit interface; for a free 
surface residue  the replacement matrix might be greater. A second observation is 
that Trp, which one might expect to be readily replaceable by Tyr or Phe, is not 
(according to the Bordo and Argos paper I cited). Trp most often changes with Tyr, 
but only in buried locations. Nonetheless, in aligned sequences of the ATP
synthase beta subunit we found one position where a conserved R changes to W in 2/9 
instances, and an in vitro R->W mutation was successful. I haven't modeled this 
change, but I expect that W, in this instance, is comparable to R in space-filling,
polarity, and H-bonding (and other properties of which I'm ignorant).

|  Peter Gegenheimer                          |  pgegen at kuhub.cc.ukans.edu      |
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