Subject: Re: CCL:accessible atom or residues on protein surface

From: [email-masked]
Date: Thu, 2 Aug 2001 18:10:12 -0500

Hello --

Regarding the issue of identifying atoms/residues on the solvent
accessible surface of a protein, [email-masked] (Minghu) wrote:

> I had tried the several softwares to calculate the solvent accesible 
> area or relative %area of per atom or residue. But in order to pick 
> out those groups on the protein surface, I also have to define a 
> threthod value for the surface area. (for example, let is say, if 
> the surface area of one certain residue is larger than 30%, we can 
> assume the residue is on the protein surface.) So my question will 
> turn into :    how large will this reasonable value roughly be? 
> ( from the view of biochemistry and chemistry)
>
> Of course I can try some arbitrary values, select out the assumed 
> suface group and finally check them by comparing with some 
> general-used softwares.But since I just began my work, so I am very
> interested in know whether any previous works/references about this
> question or are there any other methods instead of calculating 
> solvent accesible areas.

Dr. Felix Deanda (a former grad student, now at GlaxoSmithKline/RTP)
and I have recently submitted a manuscript on this subject and I would
be glad to provide pre-prints.  Meanwhile, here are a few very brief 
comments in response to Minghu's inquiry:

> are there any other methods instead of calculating 
> solvent accesible areas.

We reviewed the literature and tested five methods for identifying
the surface atoms of macromolecules.  The method based on calculating
atomic contributions to the surface area was, *by far*, the best.  We
also demonstrated that using efficient software for the surface area
(or solvent accessible surface area) calculation yields results in
very acceptable cpu times (less than 10 seconds on a modest PC).

> I had tried the several softwares to calculate the solvent accesible 
> area or relative %area of per atom or residue.

Most applications requiring (or benefitting from) a specification of
the "protein surface" would be best served by a list of "surface atoms"
as opposed to a list of "surface residues".

> But in order to pick 
> out those groups on the protein surface, I also have to define a 
> threthod value for the surface area.
> ...
> how large will this reasonable value roughly be? 
> ( from the view of biochemistry and chemistry)

We explicitly addressed the issue of a threshold surface area value 
for distinguishing "surface atoms" from "interior atoms".  Clearly,
any atom with non-zero surface area is a "true surface atom."  The
issue boils down to asking "How much of the true surface am I willing
to ignore?"  Using a-chymotrypsin (6CHA) as an example:

threshold (A^2):   0.010    0.025    0.250    1.000    2.500
% total Area:    100.000   99.998   99.902   99.266   97.430
% total atoms:    53.16    52.65    48.15    41.37    34.64

Averaged over six proteins of diverse size and shape (6CHA, 1RA2, 
3FXN, 7TLN, 1TIM, 3TRA), our recommended threshold value of 1.0 A^2
yields 99.16% of the true surface areas. 

> how large will this reasonable value roughly be? 
> ( from the view of biochemistry and chemistry)

If one were developing some sort of surface-based model of some
protein-related property, weighting the contributions of "surface 
atoms" according to their actual surface areas seems to be the best
way to address what Minghu probably had in mind when he added 
"from the view of biochemistry and chemistry".

I hope my comments have been helpful.

  -- Bob

Robert S. Pearlman, Ph.D
Coulter R. Sublett Regents Chair in Pharmacy and
Director, Laboratory for the Development of
  Computer-Assisted Drug Discovery Software
College of Pharmacy
University of Texas
Austin, Texas 78712
512-471-3383 (voice)
512-471-7474 (FAX)
[email-masked]