Protein surface interpretation - help

Stefek Borkowski stefek at killspam.edu
Thu Oct 7 08:23:42 EST 2004

```Dr Engelbert Buxbaum wrote:
> 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/.