[gmx-users] large error bars in PMF

[Justin A. Lemkul]

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
> 
> 
> 
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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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