Protein surface interpretation - help

Dr Engelbert Buxbaum engelbert_buxbaum at hotmail.com
Thu Oct 7 07:59:48 EST 2004


Stefek Borkowski wrote:

> The fundamental question for me, however, is whether the solvent accessible
> surface area of a protein is the right choice to calculate the number of
> potential antibody binding sites (i.e. the sites that can be bound at the
> same time, skipping considerations of spatial hinderance between
> antibodies). In other words, could the accessible surface be assumed as the
> one interacting with antibody? If this assumption were true then I would be
> happy just calculating this: approx. 7000 (the output value for solvent
> accessible area - see below)
> divided by 1500 is equal to approx. 4 or 5 possible simultaneous binding
> sites on my protein.

The value you calculated would be some upper limit, because not all
patches of the surface will be equally immunogenic. In other words, you
calculate how many antibodies would (mechanically) fit onto the surface,
the number of potential binding sites will be lower.

> Maybe it would also help if I sent
> you the original PDB file with the crystal structure of the protein of
> interest - approx. 120 kB?

PDB-files are easily available from the internet - it is thus sufficient
to just give the PDB-number, as you have done.

> P.S. Below is the summary from the output of my calculating software.

Small differences between values are to be expected and result from
different implementations. 

Additionally, there is the problem of non-integer dimension of the
protein surface: Because the surface of a protein is not smooth, but has
protrusions and groves, its area is not a purely 2-dimensional value.
Mathematically, you can assign it a dimensionality between 2 and 3, thus
it is something between a surface and a volume. This is called a fractal
dimension, and is topic of fractal mathematics (you may have seen the
beautiful plots of Mandelbrodt- and Julia-sets, which are also
fractals). 

Thus if you want to assign a 2-dimensional value "area" to the surface,
the result depends on how fine a ruler you apply, as the ruler becomes
finer, the area will move towards infinity. Of course one can argue that
for practical purposes rulers smaller than the diameter of a hydrogen
atom will not be useful, and that is essentially what your programs use.

> 
> And now what is that "CONTACT AREA"?! Is it the same as "molecular area"? If
> so, is such a huge difference between solvent accessible area and molecular
> area possible then?! Looks improbable...

The definitions should be in the documentation that comes with the
programs. As I had to deleted my Linux-stuff due to interference with my
Windoze-installation, I can not check right now. 

A good way to learn about basic molecular modelling is the
Protein-Explorer, http://www.umass.edu/microbio/chime/.



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