Hi Amy,
thank you so much for the message.
1- Assuming that without the receptor the same POPC bilayer looks very
stable under the same conditions
2- In charm36 ff the bilayer the same system looks very stable during
all of the simulation (I just have checked it on the system prepared
in charm-gui and run in Amber16)
3- Nothing happens with the conformation of the protein althought it
was simulated on a short timescales ~ 30 ns.
Tomorrow a new *friday* movie will be available showing a strange
things of the lipids happened just after all the restraints from the
proteins were removed.
James
2017-08-31 17:23 GMT+02:00 Amy Rice <arice3.hawk.iit.edu>:
> 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
>> >>>>>>
>> >>>>>> _______________________________________________
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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 - 10:00:03 PDT
