[gmx-users] large error bars in PMF

Justin A. Lemkul jalemkul at vt.edu
Thu Jul 21 23:02:49 CEST 2011 


Rebeca García Fandiño wrote:
> Thanks for your answer.
> My peptide has 6 residues and it is cyclic.
> I calculated the errors through bootstrap, using this:
> 
> g_wham -it tpr-files.dat -if pullf-files.dat -o -hist -unit kCal -b 500 
> -n Bootstrap 200
> 
> Are the pmfs aligned on the minimum distance value? Is that the value by 
> default? How could I calculate the errors based on the PMFs aligned on 
> the long distance value?
> 

By default, the smallest distance along the reaction coordinate is set to an 
energy value of zero (and actually WHAM does this for each window before 
reconstructing the continuous PMF).  You can set whichever value of the reaction 
coordinate you want to take as zero with the -zprof0 option.

-Justin

> Thanks a lot for all the help.
> 
> Best wishes,
> 
> Rebeca.
> 
> 
>  > From: x.periole at rug.nl
>  > To: gmx-users at gromacs.org
>  > Subject: Re: [gmx-users] large error bars in PMF
>  > Date: Thu, 21 Jul 2011 14:33:28 -0600
>  >
>  >
>  > One potential problem you have is that as Justin mentioned your minimum
>  > is not well defined and certain much less well sampled than the long
>  > distances
>  > windows. Small peptides (depends the size) may sample relevant phase
>  > space to get reasonable convergence within 8 ns when free in solution;
>  > in contact certainly not ...
>  >
>  > How long is you peptide?
>  >
>  > You might get a better estimate of your error by plotting all the pmfs
>  > you've
>  > got through bootstrap (if this is the case) ... and get the errors
>  > based on the
>  > pmfs aligned on the long distance value and not on the "minimum" which
>  > is
>  > probably what you did ... if the minimum is not well defined then it
>  > does not
>  > make sense.
>  >
>  > On Jul 21, 2011, at 1:36 PM, Justin A. Lemkul wrote:
>  >
>  > >
>  > >
>  > > Rebeca García Fandiño wrote:
>  > >> OK,
>  > >> I will try a dodecahedral box and also to extend my actual
>  > >> simulations.
>  > >> Could you give me some advice about starting to learn about 3D PMF?
>  > >> I have not seen this in the manual, and I have never used it
>  > >> before. I have only found your tutorial about how to calculate PMF
>  > >> in Gromacs 4...
>  > >
>  > > In practice, there's basically nothing different between 3D and 1D.
>  > > You specify the dimensions to which the biasing potential is applied
>  > > with pull_dim or pull_vec (depending on the pull_geometry used).
>  > > Right now you're calculating the PMF along the z-dimension only
>  > > ("pull_dim = N N Y"), which may be appropriate for one-dimensional
>  > > processes or those in which the reference group does not rotate much
>  > > in the timeframe of the sampling. Setting "pull_dim = Y Y Y" will
>  > > apply the restraint in all dimensions.
>  > >
>  > > -Justin
>  > >
>  > >> Thanks a lot again for your help.
>  > >> Best wishes,
>  > >> Rebeca.
>  > >> > Date: Thu, 21 Jul 2011 15:16:52 -0400
>  > >> > From: jalemkul at vt.edu
>  > >> > To: gmx-users at gromacs.org
>  > >> > Subject: Re: FW: [gmx-users] large error bars in PMF
>  > >> >
>  > >> >
>  > >> >
>  > >> > Rebeca García Fandiño wrote:
>  > >> > >
>  > >> > >
>  > >> > > I am trying to achieve the binding energy of the dimer composed
>  > >> by the
>  > >> > > two small cyclic peptides, to compare it with experimental. What
>  > >> > > advantages would I have using 3D PMF instead only 1D for this
>  > >> calculation?
>  > >> >
>  > >> > Intuitively, two molecules diffuse through solution until they
>  > >> find one another,
>  > >> > which to me sounds a lot like a 3D path. Further, using a
>  > >> dodecahedral box for
>  > >> > your umbrella sampling removes the problems you're having with
>  > >> the peptides
>  > >> > rotating. It sounds like you're trying to pull in one direction
>  > >> along a
>  > >> > rectangular box, but the peptides are not playing nice. I feel
>  > >> like this
>  > >> > discussion has come up at least once or twice before, though...
>  > >> >
>  > >> > -Justin
>  > >> >
>  > >> > > Thanks a lot!
>  > >> > > Rebeca.
>  > >> > >
>  > >> > > > Date: Thu, 21 Jul 2011 14:14:44 -0400
>  > >> > > > From: jalemkul at vt.edu
>  > >> > > > To: gmx-users at gromacs.org
>  > >> > > > Subject: Re: [gmx-users] large error bars in PMF
>  > >> > > >
>  > >> > > >
>  > >> > > >
>  > >> > > > Rebeca García Fandiño wrote:
>  > >> > > > > Hi,
>  > >> > > > > thanks a lot for your quick answer.
>  > >> > > > > What I am trying to pull are two small peptides one from
>  > >> another (r_1
>  > >> > > > > and r_2).
>  > >> > > > > I did not understand very well your last suggestion: "...if
>  > >> you want
>  > >> > > > > reasonable error bars you will not lots of well-converged
>  > >> data".
>  > >> > > >
>  > >> > > > Oops, that should have read "you will *need* lots of well-
>  > >> converged
>  > >> > > data."
>  > >> > > >
>  > >> > > > > Do you mean I will need also more windows besides extending
>  > >> the
>  > >> > > simulations?
>  > >> > > >
>  > >> > > > I doubt you need more windows. Likely you just need more time
>  > >> in each.
>  > >> > > >
>  > >> > > > > I think the problem could be also that the peptides I am
>  > >> using
>  > >> > > rotate in
>  > >> > > > > the box and they do not remain flat one respect to the
>  > >> other. They
>  > >> > > > > gyrate freely and some parts of their structure interact
>  > >> along the
>  > >> > > > > pulling...
>  > >> > > >
>  > >> > > > Interactions are part of the dissociation process and are not
>  > >> > > problematic per
>  > >> > > > se. But if you're trying to obtain only a one-dimensional PMF
>  > >> then your
>  > >> > > > rotation could be a problem. Is there some reason you need a
>  > >> > > one-dimensional
>  > >> > > > PMF and not a three-dimensional PMF? What are you trying to
>  > >> achieve?
>  > >> > > >
>  > >> > > > -Justin
>  > >> > > >
>  > >> > > > > Thanks a lot again for your help.
>  > >> > > > > Best wishes,
>  > >> > > > > Rebeca.
>  > >> > > > >
>  > >> > > > >
>  > >> > > > >
>  > >> > > > >
>  > >> > >
>  > >> 
> ------------------------------------------------------------------------
>  > >> > > > > From: regafan at hotmail.com
>  > >> > > > > To: gmx-users at gromacs.org
>  > >> > > > > Date: Thu, 21 Jul 2011 16:36:59 +0000
>  > >> > > > > Subject: [gmx-users] large error bars in PMF
>  > >> > > > >
>  > >> > > > >
>  > >> > > > > Hi,
>  > >> > > > > I am trying to calculate the binding energy of two
>  > >> molecules using the
>  > >> > > > > PMF (Umbrella Sampling method) and Gromacs 4.0.
>  > >> > > > > Some weeks ago I have written to the list because changing
>  > >> the
>  > >> > > number of
>  > >> > > > > windows used in the Umbrella Sampling calculations
>  > >> different results
>  > >> > > > > were obtained, and I was suggested to extend my simulations
>  > >> since the
>  > >> > > > > error bars associated to each windows were too high.
>  > >> > > > > I have now extended my simulations from 1 ns to 8 ns,
>  > >> however, I
>  > >> > > cannot
>  > >> > > > > see much different from the shorter calculations. I send
>  > >> you the
>  > >> > > > > comparison of the two PMF including the error bars
>  > >> (attached).
>  > >> > > > > Now I am using 50 windows, but the shorter simulations were
>  > >> done using
>  > >> > > > > 100 windows, so I don't think increasing the number of
>  > >> windows
>  > >> > > could help.
>  > >> > > > > My system has about 29200 atoms (where 29000 are chloroform
>  > >> atoms).
>  > >> > > The
>  > >> > > > > *mdp file I am using is copied below.
>  > >> > > > > Would you have any suggestion to improve the results and
>  > >> decrease the
>  > >> > > > > error bars in the calculations?
>  > >> > > > >
>  > >> > > > > ----------------------------MDP
>  > >> file---------------------------
>  > >> > > > > title = Umbrella pulling simulation
>  > >> > > > > define =
>  > >> > > > > define =
>  > >> > > > > ; Run parameters
>  > >> > > > > integrator = md
>  > >> > > > > dt = 0.002
>  > >> > > > > tinit = 0
>  > >> > > > > nsteps = 500000 ; 1 ns
>  > >> > > > > nstcomm = 10
>  > >> > > > > ; Output parameters
>  > >> > > > > nstxout = 5000 ; every 10 ps
>  > >> > > > > nstvout = 5000
>  > >> > > > > nstfout = 5000
>  > >> > > > > nstxtcout = 5000 ; every 10 ps
>  > >> > > > > nstenergy = 5000
>  > >> > > > > ; Bond parameters
>  > >> > > > > constraint_algorithm = lincs
>  > >> > > > > constraints = all-bonds
>  > >> > > > > continuation = yes
>  > >> > > > > ; Single-range cutoff scheme
>  > >> > > > > nstlist = 5
>  > >> > > > > ns_type = grid
>  > >> > > > > rlist = 1.4
>  > >> > > > > rcoulomb = 1.4
>  > >> > > > > rvdw = 1.4
>  > >> > > > > ; PME electrostatics parameters
>  > >> > > > > coulombtype = PME
>  > >> > > > > fourierspacing = 0.12
>  > >> > > > > fourier_nx = 0
>  > >> > > > > fourier_ny = 0
>  > >> > > > > fourier_nz = 0
>  > >> > > > > pme_order = 4
>  > >> > > > > ewald_rtol = 1e-5
>  > >> > > > > optimize_fft = yes
>  > >> > > > > ; Berendsen temperature coupling is on in two groups
>  > >> > > > > Tcoupl = Nose-Hoover
>  > >> > > > > tc_grps = ACH CL3
>  > >> > > > > tau_t = 0.5 0.5
>  > >> > > > > ref_t = 300 300
>  > >> > > > > ; Pressure coupling is on
>  > >> > > > > Pcoupl = Parrinello-Rahman
>  > >> > > > > pcoupltype = isotropic
>  > >> > > > > tau_p = 1.0
>  > >> > > > > compressibility = 4.5e-5
>  > >> > > > > ref_p = 1.0
>  > >> > > > > ; Generate velocities is off
>  > >> > > > > gen_vel = no
>  > >> > > > > ; Periodic boundary conditions are on in all directions
>  > >> > > > > pbc = xyz
>  > >> > > > > ; Long-range dispersion correction
>  > >> > > > > DispCorr = EnerPres
>  > >> > > > > ; Pull code
>  > >> > > > > pull = umbrella
>  > >> > > > > pull_geometry = distance
>  > >> > > > > pull_dim = N N Y
>  > >> > > > > pull_start = yes
>  > >> > > > > pull_ngroups = 1
>  > >> > > > > pull_group0 = r_1
>  > >> > > > > pull_group1 = r_2
>  > >> > > > > pull_init1 = 0
>  > >> > > > > pull_rate1 = 0.0
>  > >> > > > > pull_k1 = 1000 ; kJ mol^-1 nm^-2
>  > >> > > > > pull_nstxout = 1000 ; every 2 ps
>  > >> > > > > pull_nstfout = 1000 ; every 2 ps
>  > >> > > > >
>  > >> > > > > -----------------------------------------------
>  > >> > > > >
>  > >> > > > >
>  > >> > > > > Thanks a lot in advance.
>  > >> > > > >
>  > >> > > > > Best wishes,
>  > >> > > > >
>  > >> > > > > Dr. Rebeca Garcia
>  > >> > > > > Santiago de Compostela University
>  > >> > > > > Spain
>  > >> > > > >
>  > >> > > > >
>  > >> > > > >
>  > >> > > > > -- gmx-users mailing list gmx-users at gromacs.org
>  > >> > > > > http://lists.gromacs.org/mailman/listinfo/gmx-users Please
>  > >> search the
>  > >> > > > > archive at 
> http://www.gromacs.org/Support/Mailing_Lists/Search
>  > >> before
>  > >> > > > > posting! Please don't post (un)subscribe requests to the
>  > >> list. Use the
>  > >> > > > > www interface or send it to gmx-users-request at gromacs.org.
>  > >> Can't post?
>  > >> > > > > Read http://www.gromacs.org/Support/Mailing_Lists
>  > >> > > > >
>  > >> > > >
>  > >> > > > --
>  > >> > > > ========================================
>  > >> > > >
>  > >> > > > Justin A. Lemkul
>  > >> > > > Ph.D. Candidate
>  > >> > > > ICTAS Doctoral Scholar
>  > >> > > > MILES-IGERT Trainee
>  > >> > > > Department of Biochemistry
>  > >> > > > Virginia Tech
>  > >> > > > Blacksburg, VA
>  > >> > > > jalemkul[at]vt.edu | (540) 231-9080
>  > >> > > > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>  > >> > > >
>  > >> > > > ========================================
>  > >> > > > --
>  > >> > > > gmx-users mailing list gmx-users at gromacs.org
>  > >> > > > http://lists.gromacs.org/mailman/listinfo/gmx-users
>  > >> > > > Please search the archive at
>  > >> > > http://www.gromacs.org/Support/Mailing_Lists/Search before
>  > >> posting!
>  > >> > > > Please don't post (un)subscribe requests to the list. Use the
>  > >> > > > www interface or send it to gmx-users-request at gromacs.org.
>  > >> > > > Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>  > >> > >
>  > >> >
>  > >> > --
>  > >> > ========================================
>  > >> >
>  > >> > Justin A. Lemkul
>  > >> > Ph.D. Candidate
>  > >> > ICTAS Doctoral Scholar
>  > >> > MILES-IGERT Trainee
>  > >> > Department of Biochemistry
>  > >> > Virginia Tech
>  > >> > Blacksburg, VA
>  > >> > jalemkul[at]vt.edu | (540) 231-9080
>  > >> > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>  > >> >
>  > >> > ========================================
>  > >> > --
>  > >> > gmx-users mailing list gmx-users at gromacs.org
>  > >> > http://lists.gromacs.org/mailman/listinfo/gmx-users
>  > >> > Please search the archive at 
> http://www.gromacs.org/Support/Mailing_Lists/Search
>  > >> before posting!
>  > >> > Please don't post (un)subscribe requests to the list. Use the
>  > >> > www interface or send it to gmx-users-request at gromacs.org.
>  > >> > Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>  > >
>  > > --
>  > > ========================================
>  > >
>  > > Justin A. Lemkul
>  > > Ph.D. Candidate
>  > > ICTAS Doctoral Scholar
>  > > MILES-IGERT Trainee
>  > > Department of Biochemistry
>  > > Virginia Tech
>  > > Blacksburg, VA
>  > > jalemkul[at]vt.edu | (540) 231-9080
>  > > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>  > >
>  > > ========================================
>  > > --
>  > > gmx-users mailing list gmx-users at gromacs.org
>  > > http://lists.gromacs.org/mailman/listinfo/gmx-users
>  > > Please search the archive at 
> http://www.gromacs.org/Support/Mailing_Lists/Search
>  > > before posting!
>  > > Please don't post (un)subscribe requests to the list. Use the www
>  > > interface or send it to gmx-users-request at gromacs.org.
>  > > Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>  >
>  > --
>  > gmx-users mailing list gmx-users at gromacs.org
>  > http://lists.gromacs.org/mailman/listinfo/gmx-users
>  > Please search the archive at 
> http://www.gromacs.org/Support/Mailing_Lists/Search before posting!
>  > Please don't post (un)subscribe requests to the list. Use the
>  > www interface or send it to gmx-users-request at gromacs.org.
>  > Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
> 

-- 
========================================

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

========================================

More information about the gromacs.org_gmx-users mailing list