From: Gianluca Interlandi (gianluca_at_u.washington.edu)
Date: Tue Aug 07 2012 - 16:20:34 CDT
I'm not really an expert of how GBIS/SASA are implemented in NAMD. From
past experience I know that SASA for implicit solvent calculations is
usually optimized for speed at the cost of accuracy. I don't know whether
this applies to NAMD as well, but my feeling is that VMD will probably be
more accurate in calculating SASA than the method implemented in NAMD for
the implicit solvent calculations. But, I might need to be corrected here.
Gianluca
On Tue, 7 Aug 2012, Aron Broom wrote:
> yes, I'd agree with what Gianluca said, probably easiest to just post-process with
> VMD in order to see what is happening in your simulation. I imagine someone with
> reasonable programming skills could get the NAMD SASA code to output the SASA (either
> total or per-atom) as the program went along to some kind of trajectory file.
> Probably such a thing would take an appropriately skilled person a matter of a few
> hours to do. Sadly I'm with you Roy in that I have a poor comprehension of C++.
>
> It's still pretty quick in VMD.
>
> ~Aron
>
>
> On Tue, Aug 7, 2012 at 4:16 PM, Gianluca Interlandi <gianluca_at_u.washington.edu>
> wrote:
> 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.
> -----------------------------------------------------
>
>
>
>
> --
> 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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