[gmx-users] restraints in PMF (Justin's tutorial)
Justin A. Lemkul
jalemkul at vt.edu
Wed Jun 22 17:51:36 CEST 2011
Rebeca García Fandiño wrote:
> 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?
>
You don't. Why wouldn't two molecules rotate freely in solution when binding or
unbinding? It seems like completely natural behavior. Even in simple systems
of protein-ligand association, part of the binding energy is the entropic
restriction of the ligand into a certain binding-competent pose. Why wouldn't
that happen here? Sounds like an artificial notion to me.
-Justin
> 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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--
========================================
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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