[gmx-users] large error bars in PMF

XAvier Periole x.periole at rug.nl
Thu Jul 21 22:33:28 CEST 2011 

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
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>> > > > >
>> > > >
>> > > > --
>> > > > ========================================
>> > > >
>> > > > 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
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>> > >
>> >
>> > --
>> > ========================================
>> >
>> > 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
>> >
>> > ========================================
>> > --
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>
> -- 
> ========================================
>
> 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
>
> ========================================
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