[gmx-users] unfolding a protein
Justin A. Lemkul
jalemkul at vt.edu
Wed Feb 20 16:50:54 CET 2008
Quoting Siavoush Dastmalchi <Dastmalchi.s at tbzmed.ac.ir>:
> Hi Justi,
> Thanks for the comments. Yes, I am showing MD ~.mdp file and I know that my
> system is not neutral. I am not following the unfolding path and my intention
> by unfolding the protein is to get a conformation which I could regard it as
> one of the feasible unfolded conformations.
> Do you think, not neutralizing the system will somehow prevent unfolding?
I don't think the ions are the cause. I think your simulation time is way too
short to be seeing unfolding. I mentioned the ions because simulating a
charged system is not necessarily a real approximation of a physiological (or
in vitro) system. The world does not bear a net charge!
I would suggest adding counterions to neutralize the charge, and use PME instead
of cut-off. I think it is more reliable, based on my experience. The cut-off
method for calculating electrostatics is quicker, but I believe PME is more
> Cheers, Siavoush
> From: gmx-users-bounces at gromacs.org on behalf of Justin A. Lemkul
> Sent: Wed 2008/02/20 06:35 È.Ù
> To: Discussion list for GROMACS users
> Subject: Re: [gmx-users] unfolding a protein
> Quoting Siavoush Dastmalchi <Dastmalchi.s at tbzmed.ac.ir>:
> > Hi there,
> > I want to unfold a protein (hen egg white lysozyme) which has got 4
> > bounds. I have tried 1 ns of MD at 400 K either in vacuum or hydrated form
> > and it didn't unfold. I know it may need longer time, but it doesn't show
> > sign of even starting to unfold. I think I am restraining the protein in
> > way. Please see below the content of ~.mdp file that I use.
> My guess is that 1 ns is far too short to see any signs of unfolding.
> Typically, we think of protein folding on the microsecond - second timescale,
> so even if you speed things along by running your simulation at higher
> temperature, you should be running tens of nanoseconds, if not 100 or more.
> Check the literature to see what other people consider a reasonable time
> Also, what have you done in terms of minimization and equilibration? Are you
> showing the production MD .mdp file?
> As far as "thinking" you are restraining your protein, these are things you
> to be very sure of :-) Your topology likely specifies #include "posre.itp"
> you include a "define" statement within your .mdp file (which I don't see),
> I doubt you are restraining your protein in any way.
> > Would you please let me know how I could unfold a protein using an MD
> > simulation?
> > Do you think unfolding a water soluble protein in vacuum would be faster?
> Maybe, but what would it prove?
> As a side note, are you including counterions in your simulation? I don't
> them incorporated into your tc-grps, so I'm wondering if you have an
> electroneutral system.
> > Cheers, Siavoush
> > cpp = /lib/cpp
> > include = -I../top
> > integrator = md
> > dt = 0.002
> > nsteps = 500000
> > nstxout = 1000
> > nstvout = 1000
> > nstlog = 100
> > nstenergy = 100
> > nstxtcout = 100
> > xtc_grps = protein sol
> > energygrps = protein sol
> > nstlist = 10
> > ns_type = grid
> > rlist = 0.8
> > coulombtype = cut-off
> > rcoulomb = 1.4
> > rvdw = 1.4
> > pbc = xyz
> > tcoupl = berendsen
> > tc-grps = protein sol
> > tau_t = 0.1 0.1
> > ref_t = 400 400
> > Pcoupl = berendsen
> > Pcoupltype = isotropic
> > tau_p = 1.0
> > compressibility = 4.5e-5
> > ref_p = 1.0
> > gen_vel = yes
> > gen_temp = 400
> > gen_seed = 173529
> > constraints = all-bonds
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> Justin A. Lemkul
> Graduate Research Assistant
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul at vt.edu | (540) 231-9080
> gmx-users mailing list gmx-users at gromacs.org
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Justin A. Lemkul
Graduate Research Assistant
Department of Biochemistry
jalemkul at vt.edu | (540) 231-9080
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