Subject: CCL:Summary: Hydrophobic surface area

From: Torben Rasmussen <Torben.Rasmussen^at^kemi.uu.se>
Date: Wed, 6 Oct 2004 17:16:35 +0200

Hi,

I would like to thank a series of people for very valuable pointers 
about hydrophobic surface area evaluation. The people are (in no 
prioritized order):
Mitchell Polley, Jamie Platts, Andreas Bender, Joe, Rajarshi Guha, 
Giulio Vistoli, Gabriele Cruciani, and Michel Petitjean.

I haven t had a chance to test the various alternatives yet, so I might 
get back to some of you to obtain the scripts and code that you have 
kindly offered to provide me with.

I think, that I will initially test GRID, but I may eventually also 
test some of the other proposed alternatives.

Thanks again,
Torben.

Here are all the answers I received:
Mitchell Polley:
I'd recommend MolCAD by Jurgen Brickman, available from Tripos Inc. 
(www.tripos.com)

Jamie Platts:
I can send a copy of Dodd and Theorodou's original VOLUME program, 
which treats molecules as a set of super-imposed vdw spheres and 
reports their exposed surface area (see reference below).
We've also modified this to read MDL mol files, and automatically 
identify polar (N, O, NH, OH) atoms, if this would be useful. Both are 
freely distributed under the GNU GPL.
Reference:
"Analytical treatment of the volume and surface area of molecules 
formed by an arbitrary collection of unequal spheres intersected by 
planes"
L.R. Dodd and D.N. Theodorou
MOLECULAR PHYSICS, Volume 72, Number 6, 1313-1345, April 1991

Andreas Bender:
One possibility is GRID (http://www.moldiscovery.com/) - which is free 
for academic research groups. You can calculate points on the surface 
e.g. using msms and then use the coordinates as input for GRID, in 
combination with suitable probes (e.g. methyl or DRY probe in your 
case) put at those points you get estimates about "hydrophobicity" 
(energy values) in certain areas of your molecule. I wrote a tcsh 
script to calculate those energy values in bath mode and I could send 
it to you. Just be aware that you need to have msms and GRID installed 
for it to run.

Joe:
One of the easiest approaches is to take Ertl's TPSA rules to calculate 
polar surface area and consider everything else as lipophilic (total 
area - TPSA). If you want graphical representations, I think Molcad 
does this...

Rajarshi Guha:
HSA descriptors (as well as surface area and molecular volume) are 
available in the ADAPT package (http://research.chem.psu.edu/pcjgroup/)

Giulio Vistoli:
I can suggest to use VEGA program (www.ddl.unimi.it) It is free and can 
calculate polar surface area and total area and by difference you can 
have an evaluation of hydrophobic surface.

Gabriele Cruciani:
Try GRID, with DRY (hydrophobic) probe, for small molecules and 
biomolecules as well.
It is free. Windows UNIX and Linux are available, under 
www.moldiscovery.com

Michel Petitjean:
Look to the freeware ASV (there is documentation and references):
http://petitjeanmichel.free.fr/itoweb.petitjean.spheres.html
http://petitjeanmichel.free.fr/itoweb.petitjean.freeware.html#ASV
Both the analytical method and the Monte-Carlo are included.