Subject: RMSD of sidechain

From: Liu Zhijie <[email-masked]>
Date: Mon, 16 Mar 1998 16:53:39 -0800 (PST)

Dear CCLers,

  I am looking for some advice on RMSD calculation of protein 
sidechains.As we know,sidechains placement mostly is based on
fixing the backbone atoms.Some papers evaluate the result with RMSD 
value.However I am not sure whether they calculate the value include the 
backbone atoms(since it will decrease the value greatly).Any suggestions 
will be appreciated.

  Sincerely yours,

  Elmer

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From: Rick Venable <[email-masked]>
Date: Mon, 16 Mar 1998 12:05:22 -0500 (EST)

> backbone atoms(since it will decrease the value greatly).Any suggestions 

In a well written paper, the Methods section should clearly define the
atom groupings used in the analysis, such as whether or not backbone atoms
are included.  If several people have read the paper more than once and it
still isn't clear, a polite e-mail to the cooresponding author can
sometimes help answer the question.

In doing your own calculations of sidechain RMSD, one thing to be careful
of is the exchange of equivalent carbons.  Residues where this can be a
problem include PHE and TYR.  Equivalent carbons can change places without
affecting the interior packing or conformation..  Including these aromatic
carbons in the RMSD calc can give you artificially high results; a TYR
ring flip of 180 deg is exactly the same, but most software packages
uniquely identify each carbon, e.g. CG1 and CG2 for the 2 carbons at the
'gamma' position.  These atoms should either be excluded from the RMSD
calcs, or one should check or allow for degenerate conformations.  A
similar situation exists for LEU and VAL, although the equivalence is
inexact and an exchange of methyl positions does imply a different
sidechain conformation; including CB (beta) should account for this,
however.

--
Rick Venable                  =====\     |=|    "Eschew Obfuscation"
FDA/CBER Biophysics Lab       |____/     |=|
Bethesda, MD  U.S.A.          |   \    / |=|  ( Not an official statement or
[email-masked]  |    \  /  |=|    position of the FDA; for that,
http://nmr1.cber.nih.gov/           \/   |=|    see   http://www.fda.gov  )
http://www.erols.com/rvenable

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From: "Peter Shenkin" <[email-masked]>
Date: Mon, 16 Mar 1998 14:35:51 -0500

On Mar 16, 12:05pm, Rick Venable wrote:
> Subject: CCL:RMSD of sidechain
> are included. ...
> problem include PHE and TYR. 

Yup.

In our paper on the subject (Proteins, 26:323-352 (1996)), we attempt
a comparison with previously published work.  One thing we compare
is RMSD of the sidechains.  We felt (and feel) strongly that the backbone
atoms -- including CB -- should not be included, since the positions
of these atoms are determined by phi, psi and omega, but not by the
chi (sidechain) angles.  Including CB and other backbone atoms in
the RMSD computation artificially lowers the reported RMSD (makes the
results look too good), assuming the backbone is held fixed in
the computation.

In our comparisons, we went to some lengths (perhaps it would be
an exaggeration to claim "great lengths") to make sure we were comparing
our results properly with those of other authors.  There were a few
situations, only, in which we could not figure out from a careful
reading what the other authors had used as a convention.  I believe
we give this information in the Discussion part of our paper.  I might
add that one referee took us to task for misrepresenting one of the
other authors' convention;  however, we were able to show that the
referee was incorrect.

Incidentally, no authors, as far as I am aware, have included more
than CB in this sort of work.  Including CB lowers the RMS by
SQRT( n / (n+1) ), where n is the number of atoms beyond CB.  This
factor ranges from .95 for tryptophane (n=9) to .71 for serine (n=1),
assuming that no hydrogens are included explicitly.

The above pertains to situations in which the backbone is held
fixed and the sidechains only are varied.  For modeling efforts 
in which the backbone is also permitted to move, it may be appropriate
to include backbone atoms in RMSD;  still, since backbone atoms are
likely to move only a little bit (assuming a homology modeling
approach, rather than a de-novo folding approach), I'd prefer to
see an RMSD superposition of backbone atoms only; then, based on
this superposition, seperate RMSDs for backbone atoms (including CB)
and sidechains (excluding CB).  In the limit of zero backbone motion,
this would give 0 Angs. RMSD for the backbone and the same RMSD
measure proposed above (i.e., excluding CB) for the sidechains.

	-P.

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