Hi James,
I think it is unlikely that this is just a visualization issue. Which lipid
type are you using? It looks to me like you could be experiencing a phase
transition, something I've seen happen in my simulations with DPPE under
similar simulation conditions. Have you tried simulating the bilayer
without GPCR to see if the same behavior occurs? This would be my first
step if you haven't done so already. You might also try simulating the
system in AMBER using the C36 force field (very easy to convert charmm to
amber with the chamber command in parmed) to see if this behavior is force
field dependent or not. One last though- perhaps this bilayer thickening is
an expected behavior. I haven't done much work with membrane-bound
proteins, but I suspect a significant hydrophobic mismatch between the
protein/bilayer could lead to a local bilayer thickening near the protein.
To see if this is the case, I would simulate the protein in a larger
bilayer patch, then use something like MEMBPLUGIN in VMD (
https://sourceforge.net/p/membplugin/wiki/Home/) to see if local thickening
is occurring. Hope this gives you some ideas!
- Amy
On Thu, Aug 31, 2017 at 9:52 AM, James Starlight <jmsstarlight.gmail.com>
wrote:
> update:
>
> :-)
>
> I have prepared another GPCR system and changed the equilibration
> params with very big tau_p for equilibration period which was set
> around 5ps. Visually the system looked the same - deformation of the
> bilayer along the plane parallel to its normal, just after all of the
> restrains were removed from the protein.
>
> MB it is some visualization issue due to the PBC artifacts ??
> What commands for cpptraj I should provide to remove periodicity
> correctly for the lipid-bilayer system?
> Now I am just using: trjout trajectory.trr trr nobox which produce
> such unpleasant picture.
>
>
>
> 2017-08-25 23:26 GMT+02:00 James Starlight <jmsstarlight.gmail.com>:
> > up:
> >
> > so the proposed solutions to resolve the problem of lipid
> > equilibration shown on the video:
> >
> > - increase time of the restrained simulation to allow lipids better
> > pack around the protein
> >
> > - change tau_t or tau_p constants.
> > E.g in Langevin's dynamics lower tau_t should give more stabile system
> > (because we increase the friction which should be = mass/ tau_t)
> > What's about tau_p for berendsen barostat?
> >
> > P.S. Does the GPCR inserted good in the membrane? Here I did it via
> > Charm-gui prediction a position of receptor within the lipids from OPM
> > data-base.
> >
> > James
> >
> > 2017-08-23 17:50 GMT+02:00 James Starlight <jmsstarlight.gmail.com>:
> >> I make visualization of the problem in form of movie
> >> https://youtu.be/ImgtLtV3Yk4
> >>
> >> here what I have described in the previous post happens after 5 sec
> >> of the movie at the moment when all restraints are released from the
> >> protein.
> >> During the first part of the movie only the backbone are restrained.
> >>
> >> It looks like some option set wrong like compressibility or pressure
> >> along XY dim for semi-anisotropic coupling or something else ?
> >>
> >> Here the params of the simulation:
> >>
> >>
> >> &cntrl
> >> imin=0, ! Molecular dynamics
> >> ntx=5, ! Positions and velocities read formatted
> >> irest=1, ! Restart calculation
> >> ntc=2, ! SHAKE on for bonds with hydrogen
> >> ntf=2, ! No force evaluation for bonds with hydrogen
> >> ntr=0,
> >> tol=0.0000001, ! SHAKE tolerance
> >> nstlim=5000000, ! Number of MD steps
> >> ntt=3, ! Langevin dynamics
> >> gamma_ln=1.0, ! Collision frequency for Langevin dyn.
> >> temp0=310.0, ! Simulation temperature (K)
> >> ntpr=5000, ! Print to mdout every ntpr steps
> >> ntwr=5000, ! Write a restart file every ntwr steps
> >> ntwx=5000, ! Write to trajectory file every ntwc steps
> >> dt=0.002, ! Timestep (ps)
> >> ntb=2, ! Constant pressure periodic boundary conditions
> >> barostat=1,
> >> ntp=3, ! Semi-Anisotropic pressure coupling
> >> pres0=1.0, ! Target external pressure, in bar
> >> taup=0.5,
> >> csurften=3,
> >> gamma_ten=0.0,
> >> ninterface=2,
> >> cut=10.0, ! Nonbonded cutoff (Angstroms)
> >> ioutfm=1, ! Write binary NetCDF trajectory
> >> ntxo=2, ! Write binary restart file
> >> iwrap=1,
> >> restraint_wt=0.0, restraintmask='.CA,C,O,N'
> >> /
> >> &ewald
> >> skinnb=5, ! Increase skinnb to avoid skinnb errors
> >> /
> >>
> >> 2017-08-22 16:26 GMT+02:00 James Starlight <jmsstarlight.gmail.com>:
> >>> update:
> >>>
> >>> something strange still happens during an equilibration :-)
> >>>
> >>> I am doing NPT equilibration with berendsen barostat, during 10 ns
> >>> with the restrains on the protein's side-chains (its strength is
> >>> gradually decreased):
> >>>
> >>> ntb=2, ! Constant pressure periodic boundary conditions
> >>> ntp=3, ! Semi-Anisotropic pressure coupling
> >>> pres0=1.0, ! Target external pressure, in bar
> >>> taup=0.5,
> >>> csurften=3,
> >>> gamma_ten=0.0,
> >>> ninterface=2,
> >>>
> >>> Everything OK with the system, the area-per lipids in around 80
> >>>
> >>>
> >>> In the next 10 ns I continue to use the same protol of equilibration
> >>> but without of any restraints. From this point the system looks really
> >>> strange. It starts to change its dimensions rapidly along Z dimension,
> >>> the area per lipids is drooped to 60 and becomes stable. From the
> >>> visual perspective systems looks VERY elongated along Z (as compared
> >>> to GROMACS simulations or CHARM-gui based runs with CHARM36 ff of the
> >>> same system run in Amber).
> >>>
> >>>
> >>> Any suggestions?
> >>>
> >>> James
> >>>
> >>> 2017-08-18 16:51 GMT+02:00 ABEL Stephane <Stephane.ABEL.cea.fr>:
> >>>> James,
> >>>>
> >>>> There is not a general response. For instance you could do these steps
> >>>>
> >>>> 1) Equilibrate your system with position restraints applied on the
> protein only, say 50 - 100 ns in a semisotropic pressure
> >>>> and check the x,y and z box length values. Are they stable ? if yes
> -> step 2. If not continue step 1
> >>>> 2) Equilibrated your system with NO position restraints, say 50 ns
> in a semisotropic pressure scheme and and check the x,y and z box length
> values. Are they stable? if yes -> step 3 . if not If not continue step 2
> >>>> 3) Equilibrated your system with NO position restraints, say 50ns of
> MD in anisotropic pressure and and check the x,y and z box length values.
> Are they stable ? If yes ---> you got it and you can start the production
> run. If not continue the step 2
> >>>>
> >>>> HTH
> >>>>
> >>>> Stéphane
> >>>>
> >>>>
> >>>> ________________________________________
> >>>> De : James Starlight [jmsstarlight.gmail.com]
> >>>> Envoyé : vendredi 18 août 2017 16:33
> >>>> À : AMBER Mailing List
> >>>> Objet : Re: [AMBER] An equilibration of the membrane protein prepared
> by charmm-gui
> >>>>
> >>>> Hi Stephane,
> >>>>
> >>>> how long the restraint are applied in you case on the protein (all
> >>>> atoms and bb only) during the equilibration? As I have said, I noticed
> >>>> the changing og the membrane thickness (correlated with an area per
> >>>> lipid) only when I remove ALL posres from the protein ...
> >>>>
> >>>> James
> >>>>
> >>>> 2017-08-18 16:28 GMT+02:00 ABEL Stephane <Stephane.ABEL.cea.fr>:
> >>>>> Hi James,
> >>>>>
> >>>>> In general I use the Berendsen barostat in my MD during the first
> stage of the equilibration stage since it more stable and then switch to MC
> barostat when the system is stable.
> >>>>>
> >>>>> As I said, it is preferable to perform the equilibration stage in
> semisotropic pressure to obtain a well equilibrated system and switch to
> anisotropic pressur when you system is stable It is particularly if the
> initial configuration of the system is not really good ( CHARMM-GUI). Keep
> in mind that was initially create for doing simulations with CHARMM and not
> Amber.
> >>>>>
> >>>>>> 2) Is it correct to turn off all restraints on the protein during
> equilibration?
> >>>>> Depend of the system. But in general I restrain the protein at the
> beginning of the equilibration stage and then remove the restrain, when
> your system seems to be well equilibrated and then redo an equilibration
> without restrain
> >>>>>
> >>>>> HTH
> >>>>>
> >>>>> Stephane
> >>>>>
> >>>>> ________________________________________
> >>>>> De : James Starlight [jmsstarlight.gmail.com]
> >>>>> Envoyé : vendredi 18 août 2017 15:36
> >>>>> À : AMBER Mailing List
> >>>>> Objet : Re: [AMBER] An equilibration of the membrane protein
> prepared by charmm-gui
> >>>>>
> >>>>> Thanks, Stéphane!
> >>>>>
> >>>>> Yep, the Charm-gui protocol for AMBER (using Charmm params) also
> >>>>> proposes usage of Anisotropic scaling for equilibration and
> prod.runs.
> >>>>> Also Charm-gui proposes to use MC barostat (as opposed to Berendsen
> >>>>> which I am always using).
> >>>>>
> >>>>> The questions -
> >>>>> 1)Might the semi-anisotropic scaling with Berendsen thermostat (like
> >>>>> proposed in Tutorial) be more stable for the equilibration of the
> >>>>> membrane made via Lipid14 ?
> >>>>>
> >>>>> 2) Is it correct to turn off all restraints on the protein during
> >>>>> equilibration? I have noticed that membrane start to change its
> >>>>> dimensions just after I realize all restraints from the protein (or
> >>>>> apply only very weak on the side-chains).
> >>>>>
> >>>>> Regards,
> >>>>>
> >>>>> James
> >>>>>
> >>>>> 2017-08-18 12:30 GMT+02:00 ABEL Stephane <Stephane.ABEL.cea.fr>:
> >>>>>> Hello James,
> >>>>>>
> >>>>>> You have this error because of your membrane is not enough
> equilibrated . In my experience it may take a long time (>100 ns) to have a
> well equilibrated system if this this latter is constructed with CHARMM-GUI
> . So you could run a equilibration stage of your system, first in the NPAT
> ensemble during dozens ns, and switch to anisotropic ensemble (with
> lipid14) when you think (see the variations of the , x, y and z values vs.
> time) that you system is stable.
> >>>>>>
> >>>>>> Good luck
> >>>>>>
> >>>>>> Stéphane
> >>>>>> ________________________________________
> >>>>>> De : James Starlight [jmsstarlight.gmail.com]
> >>>>>> Envoyé : vendredi 18 août 2017 09:23
> >>>>>> À : AMBER Mailing List
> >>>>>> Objet : [AMBER] An equilibration of the membrane protein prepared
> by charmm-gui
> >>>>>>
> >>>>>> Dear Amber Users!
> >>>>>>
> >>>>>> I have followed Amber tutorial of the membrane protein modeling
> >>>>>> embedded in Charmm-gui prepared membrane. On the 6ns of the
> >>>>>> unrestrained equilibration my systems has been crashed with
> following
> >>>>>> error:
> >>>>>>
> >>>>>> ERROR: Calculation halted. Periodic box dimensions have changed too
> >>>>>> much from their initial values.
> >>>>>>
> >>>>>> Your system density has likely changed by a large amount,
> probably from
> >>>>>>
> >>>>>> starting the simulation from a structure a long way from
> equilibrium.
> >>>>>>
> >>>>>> Looking on the system I have found that membrane thickness was
> >>>>>> increasing along Z direction.
> >>>>>>
> >>>>>> Question: how long equilibration should be for membrane protein
> >>>>>> embedded in charmm-gui prepared membrane ? I have checked a
> charmm-gui
> >>>>>> default protocol and found that the proposed equilibration is very
> >>>>>> short. Also they introduce a restraints on the lipids during
> >>>>>> equilibration. Is it useful approach to make it shorter?
> >>>>>>
> >>>>>> Thanks !
> >>>>>>
> >>>>>> James
> >>>>>>
> >>>>>> _______________________________________________
> >>>>>> AMBER mailing list
> >>>>>> AMBER.ambermd.org
> >>>>>> http://lists.ambermd.org/mailman/listinfo/amber
> >>>>>>
> >>>>>> _______________________________________________
> >>>>>> AMBER mailing list
> >>>>>> AMBER.ambermd.org
> >>>>>> http://lists.ambermd.org/mailman/listinfo/amber
> >>>>>
> >>>>> _______________________________________________
> >>>>> AMBER mailing list
> >>>>> AMBER.ambermd.org
> >>>>> http://lists.ambermd.org/mailman/listinfo/amber
> >>>>>
> >>>>> _______________________________________________
> >>>>> AMBER mailing list
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> >>>>
> >>>> _______________________________________________
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> >>>>
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--
Amy Rice
Ph.D. Student
Physics Department
Illinois Institute of Technology
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Received on Thu Aug 31 2017 - 08:30:04 PDT
