Re: Generalized Born Solvent Question

From: Roy Fernando (
Date: Tue Aug 07 2012 - 14:55:57 CDT

Hi Aron,

Hi checked the NAMD user guide for SASA but I was not able to understand
SASA's full capacity in the user guide. According to the user guide, teh
purpose of SASA in GBIS simulation is to calculate the hydrophobic energy
contribution from the implicit solvent. It is done with SASA as this energy
term is proportional to SASA.

If SASA is calculated I think it is done by determining the Solvent
Accessible Surface Area for the implicit solvent. In VMD it is possible to
measure surface area for each atom and save the points drawing the surface
area. Is this kind of calculations are possible inside NAMD? (I am
interested in observing the changes to solvent accessible surface when
proteins are subject to stress exerted from the solvent.)

The basic question I have a trouble identifying is how to select a molecule
or/and parts of the molecule performing a task similar to "atomselect" in

Following is the full SASA statement in VMD

*measure sasa 1.4 $all -restrict $SC -points sasapoints –samples 1000*

   - 1.4 is the radius of the implici solvent (water in here, but the
   value can be changed)
   - "all' the full molecule
   - "restrict" - part of the molecule
   - points option saves the coordinates of the surface points in a
   variable called "sasapoints"
   - samples is the number of points/Angstrom^2 used to sample the surface
   area (this number can be changed)

I tried to read the SASA source code but, my poor C knowledge did not help
me that much. I appreciate any suggestion that will help me to take a
step forward.



On Fri, Aug 3, 2012 at 4:21 PM, Aron Broom <> wrote:

> Hi Roy,
> Yes, when doing GBIS, there is an option "SASA" which is "off" by default,
> meaning that after doing the GBIS electrostatics, the VDW and other forces
> are then calculated and dynamics are performed. If you stipulate "SASA
> on", an additional force is applied based on solvent accessible surface
> area calculations for each atom, which has the effect of attempting to bury
> solvent accessible atoms. In theory, this should make GBIS calculations
> more accurately match explicit solvent calculations.
> It's been pointed out to me by various implicit solvent experts, that
> without the SASA correction, GBIS still tends to recapitulate behaviours
> such as proteins burying hydrophobic groups in their cores, because the
> breaking of weak hydrophobic VDW interactions are not compensated by any
> solvent VDW interactions. Nevertheless, from what I've seen with both
> ligand binding and protein folding simulations, applying the SASA
> correction is fairly critical for getting the correct energies from free
> energy calculation methods, and also gets protein structures that more
> accurately reflect known crystal or solution structures (my own experience
> anyway).
> In AMBER 11 the SASA correction wasn't supported when using the GPU, but
> it is now in AMBER 12. In NAMD 2.9 if one does normal GBIS on say a 2000
> atom protein (~150 amino acids) the speed on a typical M2070 (GTX570
> equivalent) GPU is ~15 ns/day, but adding in the SASA calculation drops it
> to ~5 ns/day, which I believe is because the SASA calculations are still
> performed on the CPU, whereas the GBIS calculations recently (after NAMD
> 2.8) migrated to the GPU. I haven't had a chance to play with AMBER 12, so
> I can't actually be certain that with everything on the GPU the SASA
> corrected simulation will be nearly the same speed as without, but my
> suspicion is that it will.
> As far as documentation, it's in the 2.9 user guide. Just open the PDF
> and do a search for GBIS, it should bring you to the correct section. They
> reference in their the LCPO (Linear Combination of Partial Overlaps) method
> that is used for calculating SASA. This is the same method that AMBER
> uses, but I believe GROMACS uses a different method. I'm not sure which
> method VMD uses when you invoke a SASA calculation through the TK console,
> probably that is in the relevant documentation also.
> If you're looking for the SASA source code, I was peeking into it
> recently, and I think the c file is named in such a way that it's hard to
> miss or confuse with other codes.
> ~Aron
> On Fri, Aug 3, 2012 at 3:07 PM, Roy Fernando <> wrote:
>> Hi Aron,
>> Did you refer to "Solvent Accessible Surface Area" by SASA?
>> Can we do this measurement in NAMD, in GBIS? I am intrigued!
>> Is there any documentation about using SASA in GBIS?
>> Regards,
>> Roy
>> On Mon, Jul 30, 2012 at 6:06 PM, Aron Broom <> wrote:
>>> Just as an FYI to anyone who has this same question and discovers this
>>> thread, Dr. David Case informs me that once the Generalized Born
>>> calculations have taken place, all of the atoms are effectively chargeless,
>>> since the electrostatic portion of the calculations are done, and
>>> therefore, it is safe to treat SASA equally for all of them.
>>> ~Aron
>>> On Thu, Jul 19, 2012 at 2:34 PM, Aron Broom <> wrote:
>>>> Hi Everyone,
>>>> I've asked before about the SASA term with GBIS simulations, but I'm
>>>> still slightly confused and have what I think is a rather quick question:
>>>> So I understand that in a GBIS simulation without SASA, the lack of
>>>> potential VDW interactions between water and say a hydrophobic sidechain,
>>>> means that the sidechain will tend to favour interacting with the protein,
>>>> thereby giving a partial hydrophobic effect. Moreover, when one adds in
>>>> the SASA term, the energy gradients tend to favour burial of exposed
>>>> surfaces, ideally, recapitulating in full the hydrophobic effect. What I
>>>> don't understand, is that in my reading of the articles presenting these
>>>> methods, I don't see anything about the polarity of the atoms being taken
>>>> into account for this SASA term. To me, this would suggest that a solvent
>>>> accessible polar group is just as unfavourable as a similarly exposed
>>>> hydrophobic group as far as SASA is concerned. Furthermore, because
>>>> enthalpic interactions between polar groups are stronger than between
>>>> hydrophobic groups, this would imply that if one ran a GBIS + SASA
>>>> simulation of a protein for long enough, you'd end up with a "native state"
>>>> in which the polar groups were all buried in the core.
>>>> There must be something critical I'm missing here?
>>>> ~Aron
>>>> --
>>>> Aron Broom M.Sc
>>>> PhD Student
>>>> Department of Chemistry
>>>> University of Waterloo
>>> --
>>> Aron Broom M.Sc
>>> PhD Student
>>> Department of Chemistry
>>> University of Waterloo
> --
> Aron Broom M.Sc
> PhD Student
> Department of Chemistry
> University of Waterloo

This archive was generated by hypermail 2.1.6 : Tue Dec 31 2013 - 23:22:22 CST