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: [email protected]
> To: [email protected]
> 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: [email protected]
> > > To: [email protected]
> > > CC: [email protected]
> > > 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: [email protected]
> > > > 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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