Re: Generalized Born Solvent Question

From: Aron Broom (broomsday_at_gmail.com)
Date: Tue Aug 07 2012 - 16:10:05 CDT

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

This archive was generated by hypermail 2.1.6 : Mon Dec 31 2012 - 23:21:54 CST