Re: Generalized Born Solvent Question

From: Gianluca Interlandi (gianluca_at_u.washington.edu)
Date: Tue Aug 07 2012 - 15:16:04 CDT

Roy,

I think that you are confusing two things. SASA in NAMD is used internally
to perform simulations in implicit solvent, whereas SASA in VMD is used to
analyse trajectories. I doubt that there is a way to have NAMD output the
SASA for specific atoms while the simulation is running. You have to use
VMD for that while post-processing the trajectories.

Gianluca

On Tue, 7 Aug 2012, Roy Fernando wrote:

> 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 VMD.
>  
> 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.
>  
> Regards,
>  
> Roy
>  
>  
>
>  
> On Fri, Aug 3, 2012 at 4:21 PM, Aron Broom <broomsday_at_gmail.com> 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 <roy.nandos_at_gmail.com>
> 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 <broomsday_at_gmail.com> 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
> <broomsday_at_gmail.com> 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
>
>
>
>

-----------------------------------------------------
Gianluca Interlandi, PhD gianluca_at_u.washington.edu
                     +1 (206) 685 4435
                     http://artemide.bioeng.washington.edu/

Research Scientist at the Department of Bioengineering
at the University of Washington, Seattle WA U.S.A.
-----------------------------------------------------

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