FW: [gmx-users] large error bars in PMF

Justin A. Lemkul jalemkul at vt.edu
Thu Jul 21 21:16:52 CEST 2011 


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
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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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