From: Mert Gür (gurmert_at_gmail.com)
Date: Tue Apr 21 2009 - 02:49:19 CDT
Dear Axel thanks again for your insightfull answer. I really appreciate your
help.
But shouldn't I be able to define a PMF along any reaction coordinate I
want? I mean considering different unbinding pathways I should be able to
define a PMF for each case.
>From what you are explaining I conclude that I either should perform
multidimensional WHAM (which I have to figure how to do) or somehow define
a reaction coordinate from which it wont deviate.
Do you have any suggestion how to define that. Because that means that in my
case I can' t perform US along the pulling direction I have performed for
previously in my SMD simulations (Jarzynski).
Best,
Mert
On Mon, Apr 20, 2009 at 4:41 PM, Axel Kohlmeyer <akohlmey_at_cmm.chem.upenn.edu
> wrote:
> On Mon, 2009-04-20 at 11:16 +0300, Mert Gür wrote:
> > Sorry I didn't explain my problem properly.
> > As you emphasized I divided my reaction coordinates into bins. At each
> > specific coordinate (bin), I have to aplly an biasing potential to
> > keep it there. For that case I am using SMD and set the velocity to
> > zero. So I have an harmonic potential applied along my reaction
> > coordinate(x axis). But it does not stay on the SMD vector (1 0 0). As
> > you already mentioned it samples also into the other directions (y and
> > z directions) which as far as my understanding goes (by reading the
> > literature) we don't want. That is why I applied a negligble small
>
> mert,
>
> not in my understanding. if you do umbrella sampling you should
> not constrain any other direction but the reaction coordinate.
> if your system deviates from it randomly, it should average out,
> you just have to run long enough to make sure you are converged;
> if it deviates systematically, you have chosen the wrong reaction
> path. from all you are telling us, i am tempted to believe that
> the latter is the case.
>
> cheers,
> axel.
>
> > constraining potential into the x and y directions.
> > Using the positional fluctuation values along the reaction coordinates
> > at each US simulation I construct the PMF via WHAM.
> > Best,
> > Mert
> >
> >
> > On Mon, Apr 20, 2009 at 2:27 AM, Chris Harrison <char_at_ks.uiuc.edu>
> > wrote:
> > Mert,
> >
> > I'm not sure what you mean by "SMD with zero velocity for
> > Umbrella sampling.." In typical umbrella sampling the rxn
> > coordinate is divided into bins (10 bins is usually a
> > reasonable first guess if you have no a priori knowledge of
> > how many bins are needed) and each bin is sampled
> > independently; no SMD or pulling velocity needed. You then
> > "merge" the bins to construct to PMF via a weighted histogram
> > analysis. Not sure if this helped ....
> >
> >
> > C.
> >
> >
> >
> > --
> > Chris Harrison, Ph.D.
> > Theoretical and Computational Biophysics Group
> > NIH Resource for Macromolecular Modeling and Bioinformatics
> > Beckman Institute for Advanced Science and Technology
> > University of Illinois, 405 N. Mathews Ave., Urbana, IL 61801
> >
> > char_at_ks.uiuc.edu Voice: 217-244-1733
> > http://www.ks.uiuc.edu/~char <http://www.ks.uiuc.edu/%7Echar>
> Fax: 217-244-6078
> >
> >
> > Mert Gür <gurmert_at_gmail.com> writes:
> >
> > > Date: Sun, 19 Apr 2009 19:10:11 +0300
> > > From: Mert Gür <gurmert_at_gmail.com>
> >
> > > To: Chris Harrison <char_at_ks.uiuc.edu>
> > > Cc: NAMD list <namd-l_at_ks.uiuc.edu>
> > > Subject: Re: namd-l: I can't keep my pulling directions the
> > same with the SMD
> > > vector
> > > Return-Path: char_at_halifax.ks.uiuc.edu
> >
> > > Message-ID:
> > <72cbc58f0904190910g68238254kcae57f28652acb1_at_mail.gmail.com>
> > > X-Spam-Status: No, score=-1.1 required=5.0
> > tests=AWL,BAYES_00,
> > > DNS_FROM_RFC_POST,HTML_30_40,HTML_MESSAGE,SPF_PASS
> > autolearn=no
> > > version=3.1.7-0+tcb1
> > >
> >
> >
> > > Dear Chris,
> > > It seems that my x-values increases as I wish. As you
> > suggest pulling
> > > faster with a higher force constant seems to be a solution
> > (Now I have fixed
> > > the Jarzynski case :) ) but I also try to use SMD with zero
> > velocity for
> > > Umbrella Sampling Calculations.
> > > In that case the fast pulling option wont be possible.
> > > I should somehow to be able to sample the same reaction
> > coordinates and
> > > obtain a similar PMF for both methods.
> > > Best,
> > >
> > > On Sun, Apr 19, 2009 at 6:25 PM, Chris Harrison
> > <char_at_ks.uiuc.edu> wrote:
> > >
> > > > Mert,
> > > >
> > > > You need to look at the average x-coord value. Is it
> > increasing? There's
> > > > nothing that by default restrains the pulled particle to
> > specific values of
> > > > y & z when pulling in x. So while the x-coord value may
> > increase, the
> > > > particle may in fact freely sample the available y & z
> > coordinates. The
> > > > spring constant and force constant or pulling velocity can
> > notably influence
> > > > the degree or extent to which sampling can occur in y & z
> > for a given value
> > > > of x when pulling in x. Assuming a constant velocity SMD,
> > if you pull
> > > > faster with a strong spring constant the particle will
> > "not have enough time
> > > > and spring-flexibility" to sample y & z coords that
> > significantly deviate
> > > > from those of the initial structure ... but this will of
> > course lead to
> > > > poorer sampling and possibly a noisier force curve. It is
> > a balancing act,
> > > > the "tipping point" of which must be determined
> > empirically for each system.
> > > > One approach is to do some very fast pullings to test,
> > then lower your
> > > > pulling velocity and retest, then possibly refine your
> > spring constant to
> > > > achieve an optimal "signal-to-noise" in your force curve.
> > > >
> > > >
> > > > C.
> > > >
> > > >
> > > >
> > > > --
> > > > Chris Harrison, Ph.D.
> > > > Theoretical and Computational Biophysics Group
> > > > NIH Resource for Macromolecular Modeling and
> > Bioinformatics
> > > > Beckman Institute for Advanced Science and Technology
> > > > University of Illinois, 405 N. Mathews Ave., Urbana, IL
> > 61801
> > > >
> > > > char_at_ks.uiuc.edu Voice:
> > 217-244-1733
> >
> > > > http://www.ks.uiuc.edu/~char
> http://www.ks.uiuc.edu/%
> > 7Echar>
> >
> > > > Fax: 217-244-6078
> > > >
> > > >
> > > > Mert Gür <gurmert_at_gmail.com> writes:
> > > > > Date: Sun, 19 Apr 2009 15:56:00 +0300
> > > > > From: Mert Gür <gurmert_at_gmail.com>
> > > > > To: NAMD list <namd-l_at_ks.uiuc.edu>
> > > > > Subject: namd-l: I can't keep my pulling directions the
> > same with the SMD
> > > > > vector
> > > > > Return-Path: char_at_halifax.ks.uiuc.edu
> > > > > Message-ID:
> > <72cbc58f0904190556i3ed67eecke2b3c356b1b5c2e6_at_mail.gmail.com
> > > > >
> > > > > X-Spam-Status: No, score=-2.0 required=5.0
> > tests=AWL,BAYES_00,HTML_40_50,
> > > > > HTML_MESSAGE autolearn=unavailable version=3.1.7-0
> > +tcb1
> > > > >
> > > > > I try to evaluate th PMF of unbinding of a
> > protein-protein complex. As
> > > > was
> > > > > suggested for SMD calculations in the following paper, I
> > try to move only
> > > > > into the x direction. But I just can't keep my reaction
> > coordinates
> > > > (which
> > > > > is the vector between the fixed atoms and smd atoms)
> > along the x
> > > > direction.
> > > > > I also tried to aplly an external constraining force of
> > 1/10 in magnitude
> > > > of
> > > > > the SMD spring constant. But after each simulation the
> > vector keeps
> > > > > increasing its y magnitude.
> > > > > So my question here is how high can I go with these
> > constraining forces
> > > > so
> > > > > that my reaction coordinate moves strictly along the x
> > direction and
> > > > still
> > > > > makes sense. Or is there any other methodology I missed.
> > I tried to
> > > > follow
> > > > > all the discussion that have been performed previously
> > regarding the SMD
> > > > > calculations.
> > > > > Best,
> > > > > Mert
> > > > >
> > > > > Free energy calculation from steered molecular dynamics
> > simulations using
> > > > > Jarzynski's equality Park,
> > > > > Sanghyun<
> > > > http://adsabs.harvard.edu/cgi-bin/author_form?author=Park,
> > +S&fullauthor=Park,%20Sanghyun&charset=UTF-8&db_key=PHY
> > > > >;
> > > > > Khalili-Araghi,
> > > > > Fatemeh<
> > > >
> >
> http://adsabs.harvard.edu/cgi-bin/author_form?author=Khalili-Araghi,+F&fullauthor=Khalili-Araghi,%20Fatemeh&charset=UTF-8&db_key=PHY
> > > > >;
> > > > > Tajkhorshid, Emad<
> > > >
> >
> http://adsabs.harvard.edu/cgi-bin/author_form?author=Tajkhorshid,+E&fullauthor=Tajkhorshid,%20Emad&charset=UTF-8&db_key=PHY
> > > > >;
> > > > > Schulten, Klaus<
> > > >
> > http://adsabs.harvard.edu/cgi-bin/author_form?author=Schulten,
> > +K&fullauthor=Schulten,%20Klaus&charset=UTF-8&db_key=PHY
> > > > >
> > > > >
> > > > >
> > > > > http://adsabs.harvard.edu/abs/2003JChPh.119.3559P
> > > > >
> > > > > where it is indicated that:
> > > > >
> > > > > "In the simulation, we fix one end of the molecule ~the
> > N atom of the
> > > > first
> > > > > residue! at the origin and constrain the other end ~the
> > capping N atom at
> > > > > the C-terminus! to move only along the z axis, thereby
> > removing the
> > > > > irrelevant degrees of freedom, i.e., overall translation
> > and rotation"
> > > >
> >
> >
>
> --
> =======================================================================
> Axel Kohlmeyer akohlmey_at_cmm.chem.upenn.edu http://www.cmm.upenn.edu
> Center for Molecular Modeling -- University of Pennsylvania
> Department of Chemistry, 231 S.34th Street, Philadelphia, PA 19104-6323
> tel: 1-215-898-1582, fax: 1-215-573-6233, office-tel: 1-215-898-5425
> =======================================================================
> If you make something idiot-proof, the universe creates a better idiot.
>
>
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