Re: [ccp4bb]: Protein Dimensions

[Chris Putnam <cdputnam@ucsd.edu>]

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On Thursday 21 February 2002 07:54 am, Michael Garavito wrote:
>
> Ways for determining a
> protein's dimensions from a three-dimensional structure have been written
> for analytical ultracentrifugation work (peruse
> http://www.ucc.uconn.edu/~wwwbiotc/UAF.html and associated links) in order
> to predict Stokes radii.  Unfortunately, most don't run when downloaded and
> those that do have arrays sizes that are too small (they seem to think that
> proteins are all the size of lysozyme).  

If you are simply after a Stokes radius (single value), then a lot of the 
software written for small angle X-ray scattering (SAXS) is likely to 
partially helpful.  Many of these programs (in particular CRYSOL by D. 
Svergun--check out many Acta Cryst. and Applied Crystallography pubs) will 
calculate radii of gyration (Rg), which should be similar to a Stokes radius 
(with the caveat that this is an X-ray radius which will is influenced by 
such factors as an ordered water layer (that I believe CRYSOL puts around the 
pdb input explicitly).  However, I believe it should be similar to the 
Stoke's radius (and I've pushed assemblies much larger than lysozyme through 
CRYSOL with success).

Svergun's programs can be found at:
http://www.embl-hamburg.de/ExternalInfo/Research/Sax/

More complicated descriptions could actually be generated by taking calcuated 
SAXS scattering (from say CRYSOL) and feeding them into envelope-calculating 
software (like GNOM and SASHA) so that prolate/oblate ellipsoid radii can be 
estimated, etc. (as I don't recall if CRYSOL outputs such parameters 
directly).

But my own take on Mike DiDonato's questions are somewhat different than some 
of the discussion that has occurred.  If the goal of the dimensions are to 
describe a minimal box, then AMoRe output in which the molecule is rotated 
optimally to fit in an orthogonal space to reduce number of reflections (and 
interesting use of convex hull stuff, if I remember my computational geometry 
correctly) comes to mind immediately (and has already been mentioned in this 
discussion).  But even this "orthogonal volume" is really not as good as 
actually calculating a "true" volume from the atomic model, and an orthogonal 
box view is really a poor description of the overall dimensions for many 
proteins including those that form rings or cylinders.  Thus my feeling is 
the best measurements will mostly refer to the protein in its "standard" 
orientation used in figures throughout the paper.  For globular proteins, it 
probably with have reasonably similar dimensions in each direction.  For 
non-globular proteins, the directions that are really different will be quite 
obvious to the reader, and generally will be taken into account when 
generating a non-obscured view of the overall fold.  And when using one's 
"standard orientation" to describe protein size, authors will tend to avoid 
describing things like rings with parameters other than radius and thickness.

Note that these opinions do not detract from the more general problem when 
estimating a protein volume (e.g. for analytical ultracentrifugation or SAXS 
work) or minimizing the box (e.g. for molecular replacement) are really 
useful or important.  Rather, my feeling is that a "rigorous" answer (such as 
reporting an AMoRe output of minimal box size w/rotations to put the molecule 
there) is potentially less useful than the simple graphics program 
measurements in conveying the overall protein size.  That, in the end, is 
probably the real goal that Mike is driving at and is probably why there 
hasn't really been a rigorous formulation of protein dimensions reported in 
structure papers.

C.

-- 
Christopher Putnam, Ph.D.
Ludwig Institute For Cancer Research
Cellular and Molecular Medicine East, Room 3019
9500 Gilman Drive
La Jolla, CA 92093-0660 USA
cdputnam@ucsd.edu
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