Thank you very much Aron. Your information cleared many of my doubts. What
I was specifically asking in the second part of my question was "from where
to where is r1 measured?" AND "from where to where is r4 measured?"
What I understand now is that "r1,r2,r3 and r4 all refer to the distance
between the two atoms specified by iat=atom1,atom2. As long as the distance
is between r2 and r3 (usually r2=r3 i.e harmonic) there is no restraint. As
long as the distance between the two atoms is R such that (R<r2) AND
(R>r1) a harmonic potential given by U=0.5*(rk2)*(R-r2)^2
will be applied and if (R>r3) AND (R<r4) a harmonic potential given
by U=0.5*(rk3)*(R-r3)^2 will be applied. If (R<r1) OR (R>r4) the potential
applied will be linear or constant(flat) and NOT harmonic.
I think I got it correct this time right?
Thank you
Sajeewa Dewage
On Mon, Nov 5, 2012 at 1:00 AM, Aron Broom <broomsday.gmail.com> wrote:
> Hi Sajeewa,
>
> You've got most of it correct.
>
> 1) Yes, if all the r1,r2,r3,r4 values are different the potential has a
> flat bottom, rather than being harmonic which is needed for umbrella
> sampling (at least standard umbrella sampling where you are going to use
> WHAM to build back the potential energy landscape). So yes, r2 and r3 need
> to have the same value in order to make a harmonic potential. Technically,
> a harmonic potential is only defined by its center and a force constant.
> This means that r1 and r4 are not really part of that. You have two
> options for dealing with them:
>
> A) make them far enough from the center (r2,r3) that you are confident your
> system will never venture that far, therefore your system will always see a
> harmonic well. This is not really ideal, because your assumption might be
> wrong, and then you can't use that simulation reliably for analysis.
>
> B) set them to something simple (r1 = 0, r4 = r3 + 1), and then change some
> variable (can't remember it's name right now, maybe "iat"?) so that the
> shape of the potential remains harmonic beyond r1 and r4, rather than
> becoming linear or flat (the other options for that variable). This is the
> best option, as it now means that by defining r2 = r3 = harmonic_center,
> you get the correct potential that umbrella sampling needs, regardless of
> what happens.
>
> Keep in mind for all this r1,r2,r3,r4 business, that the potential is setup
> as something more complicated than a harmonic potential, because AMBER was
> initially used to refine protein structural models (Assisted Model Building
> and Energy Refinement or something like that). So if you have NMR data
> that tells you Atom1 and Atom2 should be between 5 and 7 angstroms, you
> want any value between 5 and 7 those to have no penalty (r2 =5, r3 =7), and
> apply a penalty if they go beyond that (e.g. r1 = r2 - 2 = 3, r4 = r3 + 2 =
> 9), but if the system seems to want to go even further away from your 5 to
> 7 range, don't continue giving it a harsh harmonic penalty, but rather a
> nicer linear or flat one, because maybe your NMR data is not reliable for
> that pair of atoms.
>
> 2) None of the atoms involved in your reaction coordinate should be fixed
> if you want to properly do umbrella sampling, otherwise you are applying an
> additional bias that you can't undo later during analysis with WHAM or
> equivalent method. So, the distance restraint for instance is as you say,
> between Atom1 and Atom2 or whatever, but both of them will respond to that
> force.
>
> An additional note here, if you can (not sure what is available in AMBER12
> or whatever you are using), it's better to define groups of atoms and use
> their center mass, so for a protein ligand system, the distance might be
> between the center of mass of several heavy atoms in the protein binding
> pocket, and the center of mass of all the ligand heavy atoms. With enough
> sampling this is irrelevant, but usually one doesn't have quite enough, and
> this can help reduce noise due to other degrees of freedom like rotations
> that aren't being explicitly biased against.
>
> In response to the last thing you wrote. The distance restraint, that is,
> the harmonic potential, which will be centered at (r2 +r3)/2 and is the
> distance between Atom1 and Atom2, not anything to do with absolute
> coordinates (I'm not sure what you meant by what you wrote). So, although
> r1 and r4 are irrelevant for umbrella sampling, r1 is a value that would be
> a shorter distance, and r4 would be a longer distance between your two
> atoms).
>
> Hope that helps,
>
> ~Aron
>
> On Sun, Nov 4, 2012 at 11:32 PM, Sajeewa Pemasinghe <sajeewasp.gmail.com
> >wrote:
>
> > Hi all,
> >
> > I am new to umbrella sampling and this is the first time I am doing
> this. I
> > have some questions
> >
> > 1) The shape of the biasing potential is more or less "U" shaped if we
> give
> > four different values for r1,r2,r3 and r4 but usually to approximate a
> > harmonic shape we give the same value to r2 and r3. Am I correct?
> >
> >
> > 2) When we give distance restraints we usually write (atom#1 is fixed
> and I
> > am looking at the change in distance of atom#2 from atom#1)
> >
> > &rst iat=1,2, r1=5, r2=10, r3=10, r4=15, rk2 = 32.83, rk3 = 32.83, /
> >
> > In amber tutorial http://ambermd.org/tutorials/advanced/tutorial4/ it
> says
> > that
> >
> > "Conventionally, the violation energy is a well with a square bottom
> > between *r2* and *r3*, with parabolic sides out to a defined distance
> (*r1*
> > and *r4* for lower and upper bounds, respectively), and linear sides
> > beyond that distance"
> >
> > Does the above mean that r1 is the distance to the left (towards zero)
> from
> > r2 and r4 is the distance to the right from r3 OR are all distances
> > measured from my reference atom (atom#1 in my case)?
> >
> > I really appreciate your help.
> >
> > Thank you
> >
> > Sajeewa Dewage
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
>
>
>
> --
> Aron Broom M.Sc
> PhD Student
> Department of Chemistry
> University of Waterloo
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> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
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Received on Sun Nov 04 2012 - 23:30:02 PST
