[gmx-users] restraints in PMF (Justin's tutorial)

Rebeca García Fandiño regafan at hotmail.com
Wed Jun 22 17:32:43 CEST 2011


Thanks a lot for your quick answer!

I think they are separated enough, however my monomers are cyclic (like 
discs); I start with a parallel conformation between then, but along the
 Umbrella simulation, both of them rotate and approach.
If I do not use restraints, how could I avoid the rotation?

I am using the following md_umbrella.mdp:

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     
nstvout     = 5000
nstfout     = 5000
nstxtcout   = 5000     
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     = r_1_r_2  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 again for your help.

Best wishes,

Rebeca.

> Date: Wed, 22 Jun 2011 10:53:16 -0400
> From: jalemkul at vt.edu
> To: gmx-users at gromacs.org
> Subject: Re: [gmx-users] restraints in PMF (Justin's tutorial)
> 
> 
> 
> Rebeca García Fandiño wrote:
> > Hello,
> > I am trying to obtain the PMF from Umbrella Sampling of the process of 
> > separating two monomers of a dimer, following Justin 's tutorial
> > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html
> > 
> > I have done the Umbrella Sampling simulations without using any 
> > restraints in any of the monomers, however, I can see that they move and 
> > gyrate so that although the c.o.m are separated from each other, there 
> > are parts of both interacting, in such way that they are not separated 
> > as they should be.
> > 
> > Would it be correct if I apply restraints to both monomers in all the 
> > Umbrella Sampling simulations?. I have seen that in Justin's tutorial 
> > they applied restraints to one of the chains, but in my case I think I 
> > will need to restrain both of the units. Would that be correct for the 
> > PMF calculation?
> > 
> 
> There are no position restraints applied during the umbrella sampling 
> simulations.  They are unnecessary.  The umbrella potential is itself a 
> restraint to maintain COM separation.
> 
> If parts of your proteins are interacting, you simply haven't fully separated 
> your monomers and you need to create configurations with greater COM separation. 
>   If you apply position restraints to fit some notion that your monomers 
> shouldn't interact at certain distances, then you're applying an unnatural (and 
> potentially incorrect) bias, causing the PMF to converge incorrectly.
> 
> -Justin
> 
> > Thanks a lot in advance.
> > 
> > Rebeca.
> > 
> >  > Date: Mon, 20 Jun 2011 17:03:56 -0400
> >  > From: jalemkul at vt.edu
> >  > To: regafan at hotmail.com
> >  > CC: gmx-users at gromacs.org
> >  > Subject: Re: doubt about your Umbrella Sampling tutorial
> >  >
> >  >
> >  >
> >  > Rebeca García Fandiño wrote:
> >  > > Dear Justin,
> >  > > my name is Rebeca and I am a postdoctoral student in Santiago de
> >  > > Compostela University. Sorry for disturbing you to your personal 
> > mail, I
> >  > > have tried to post to the Gromacs-list first, but I did not get any 
> > answer.
> >  >
> >  > I was traveling and not paying much attention to messages across the 
> > list. I
> >  > will CC this reply to the list in the hopes that it is useful to 
> > others, as well.
> >  >
> >  > > I am trying to obtain the PMF from Umbrella Sampling of the process of
> >  > > separating two monomers of a dimer, following your tutorial, and I 
> > have
> >  > > a pair of doubts:
> >  > >
> >  > > 1)In this tutorial the generation of configurations is done using a 
> > .mdp
> >  > > file for pulling one chain from another, but is it possible to 
> > generate
> >  > > the configurations for Umbrella Sampling "by hand", I mean, 
> > changing the
> >  > > z coordinate of the monomer I want to move, then solvating and then
> >  > > minimizing these configurations? Is there any problem with this 
> > protocol
> >  > > for the obtaining of the configurations?
> >  > >
> >  >
> >  > No problem at all. The tutorial is but one possible method.
> >  >
> >  > > 2) I have noticed that you use restraints in the md_umbrella.mdp 
> > for the
> >  > > fixed chain. Is that correct? I can understand the restraints in the
> >  > > pulling simulations for generate starting configurations, but once you
> >  > > have the configurations, is is necessary to restrain one part of the
> >  > > system?
> >  > >
> >  >
> >  > Not usually. The tutorial presents a special case.
> >  >
> >  > > Thanks a lot in advance for your help with this topic, and thank you
> >  > > very much also for publishing this interesting tutorial. There was
> >  > > nothing useful until that for Umbrella Sampling with Gromacs 4.0, so I
> >  > > think it is more than wellcome for all Gromacs users!
> >  >
> >  > Glad they're useful :)
> >  >
> >  > -Justin
> >  >
> >  > > Best wishes,
> >  > > Rebeca.
> >  > >
> >  > > Dr. Rebeca García Fandiño
> >  > > Department of Organic Chemistry and Center for Research in Biological
> >  > > Chemistry
> >  > > and Molecular Materials
> >  > > Santiago de Compostela University
> >  > > E-15782 Santiago de Compostela (Spain)
> >  > > e-mail: rebeca.garcia.fandino at usc.es
> >  > > Phone: 34-981563100 ext 15760
> >  > >
> >  > >
> >  > >
> >  > >
> >  > >
> >  > >
> >  > >
> >  >
> >  > --
> >  > ========================================
> >  >
> >  > 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
> >  >
> >  > ========================================
> > 
> 
> -- 
> ========================================
> 
> 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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