[gmx-users] restraints in PMF (Justin's tutorial)
Rebeca García Fandiño
regafan at hotmail.com
Wed Jun 22 18:02:32 CEST 2011
OK,
I will try to increase the distances of the c.o.m of both molecules to eliminate any contact between them, adding more windows.
Thanks a lot for your help!
Best wishes,
Rebeca.
> Date: Wed, 22 Jun 2011 11:51:36 -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:
> > 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
> > >
> > > ========================================
> > > --
> > > gmx-users mailing list gmx-users at gromacs.org
> > > http://lists.gromacs.org/mailman/listinfo/gmx-users
> > > Please search the archive at
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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
> Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting!
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