[gmx-users] Combining position restraints with Parrinello-Rahman pressure coupling leads to instabilities

Naba nabajyoti.goswami at gmail.com
Tue Aug 21 08:33:24 CEST 2018


Dear Dr. Justin,

Thanks a lot for suggestions and hints.

I issued:

gmx dump -s npt.tpr

to check the velocities.

Following are last few lines after execution of the above command:

   v[120488]={-8.24012e-01, -3.10189e-01,  3.53090e-01}
   v[120489]={-5.70083e-02,  6.79958e-01,  1.43155e+00}
   v[120490]={ 4.60961e-01,  8.73407e-02, -1.26087e+00}
   v[120491]={ 3.43934e-01, -3.55264e-02,  5.41598e-02}
   v[120492]={-2.71835e-01,  2.20839e-01, -2.95827e-01}
   v[120493]={ 5.59665e-02,  6.66364e-01, -2.97680e-01}
   v[120494]={ 1.22493e-01,  5.81446e-01,  1.32195e-01}
Group statistics
T-Coupling  :   33740  86755  (total 120495 atoms)
Energy Mon. :   120495  (total 120495 atoms)
Acceleration:   120495  (total 120495 atoms)
Freeze      :   120495  (total 120495 atoms)
User1       :   120495  (total 120495 atoms)
User2       :   120495  (total 120495 atoms)
VCM         :   33740  86755  (total 120495 atoms)
Compressed X:   120495  (total 120495 atoms)
Or. Res. Fit:   120495  (total 120495 atoms)
QMMM        :   120495  (total 120495 atoms)
                                   -----

Using -maxwarn 1 in grompp, I produced the tpr file for Berendsen barostate
also and got the same output. So, I can proceed with Berendsen pressure
coupling, am I right?

Thanks & regards,
Naba




On 8/20/18 6:52 AM, Naba wrote:
> > Dear Gromacs users and developers,
> >
> > I am using Gromacs 2018.2.
> > Following the membrane protein simulation tutorial, I am planning to run
> > long simulations of a tetramer that needs larger lipid bilayer than 128
> > lipids as described in the tutorial. So, I have replicated the
> > pre-equilibrated POPC bilayer of 128 lipids from lipidbook (
> > https://lipidbook.bioch.ox.ac.uk/lipid/) to get a larger bilayer of 512
> > lipids using genconf. Moreover, I have extended gromos54a7_lipid.ff
> > forcefield to Berger lipid parameters for long membrane protein
> > simulations. I have set 10 ns for NVT and 20 ns for NPT equilibration.
> > NVT simulation ran successfully, but when I reached to NPT equilibration,
> > grompp showed me a note like the following:
> > "You are combining position restraints with Parrinello-Rahman pressure
> >    coupling, which can lead to instabilities. If you really want to
> combine
> >    position restraints with pressure coupling, we suggest to use
> Berendsen
> >    pressure coupling instead."
>
> I think this note is a bit imprecise. grompp is guessing that the
> combination of Parrinello-Rahman and restraints implies equilibration,
> and it should really say so, or otherwise do a more rigorous check to
> see if velocities are being generated. In principle, there shouldn't be
> anything wrong with this approach, but Parrinello-Rahman *usually* isn't
> the best choice for equilibration.
>

> When I used Berendsen pressure coupling, grompp terminated with a warning
> > as:
> > "Using Berendsen pressure coupling invalidates the true ensemble for the
> >    thermostat"
>
> This only matters for production runs. The Berendsen method should never
> be used for actual data collection. For equilibration, it's perfectly
> fine because you're going to throw this time out, anyway.
>
> -Justin
>
> > What to do with this? Can I proceed with the note using Parrinello-Rahman
> > pressure coupling? Please help.
> >
> > Following is the mdp parameters I have used:
> >
> > title       = NPT Equilibration for KALP15-DPPC
> > define      = -DPOSRES  ; position restrain the protein
> > ; Run parameters
> > integrator  = md        ; leap-frog integrator
> > nsteps      = 10000000    ; 2 * 10000000 = 20000 ps (20 ns)
> > dt          = 0.002     ; 2 fs
> > cutoff-scheme = verlet
> > ; Output control
> > nstxout     = 2500       ; save coordinates every 5 ps
> > nstvout     = 2500       ; save velocities every 5 ps
> > nstenergy   = 2500       ; save energies every 5 ps
> > nstlog      = 2500       ; update log file every 5 ps
> > ; Bond parameters
> > continuation            = yes       ; Restarting after NVT
> > constraint_algorithm    = lincs     ; holonomic constraints
> > constraints             = all-bonds ; all bonds (even heavy atom-H bonds)
> > constrained
> > lincs_iter              = 1         ; accuracy of LINCS
> > lincs_order             = 4         ; also related to accuracy
> > ; Neighborsearching
> > ns_type     = grid      ; search neighboring grid cels
> > nstlist     = 5         ; 10 fs
> > rlist       = 1.2       ; short-range neighborlist cutoff (in nm)
> > rcoulomb    = 1.2       ; short-range electrostatic cutoff (in nm)
> > rvdw        = 1.2       ; short-range van der Waals cutoff (in nm)
> > ; Electrostatics
> > coulombtype     = PME       ; Particle Mesh Ewald for long-range
> > electrostatics
> > pme_order       = 4         ; cubic interpolation
> > fourierspacing  = 0.16      ; grid spacing for FFT
> > ; Temperature coupling is on
> > tcoupl      = Nose-Hoover                       ; More accurate
> thermostat
> > tc-grps     = Protein_POPC  Water_and_ions      ; two coupling groups -
> > more accurate
> > tau_t       = 0.5           0.5                 ; time constant, in ps
> > ref_t       = 300           300                 ; reference temperature,
> > one for each group, in K
> > ; Pressure coupling is on
> > pcoupl      = Berendsen     ; Pressure coupling on in NPT
> > pcoupltype  = semiisotropic         ; uniform scaling of x-y box vectors,
> > independent z
> > tau_p       = 5.0                   ; time constant, in ps
> > ref_p       = 1.0   1.0             ; reference pressure, x-y, z (in bar)
> > compressibility = 4.5e-5    4.5e-5  ; isothermal compressibility, bar^-1
> > ; Periodic boundary conditions
> > pbc         = xyz       ; 3-D PBC
> > ; Dispersion correction
> > DispCorr    = EnerPres  ; account for cut-off vdW scheme
> > ; Velocity generation
> > gen_vel     = no        ; Velocity generation is off
> > ; COM motion removal
> > ; These options remove motion of the protein/bilayer relative to the
> > solvent/ions
> > nstcomm         = 1
> > comm-mode       = Linear
> > comm-grps       = Protein_POPC Water_and_ions
> > ; Scale COM of reference coordinates
> > refcoord_scaling = com
> > nstcalcenergy = 1
> > nhchainlength = 1
> >
> >
> > Thank in advance.
> >
> > Regards,
> >
> > Nabajyoti Goswami
> >
> > Research Associate
> > Bioinformatics Infrastructure Facility
> > Department of Animal Biotechnology
> > College of Veterinary Science
> > Khanapara,Guwahati 781022
> > Assam, India
>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Assistant Professor
> Virginia Tech Department of Biochemistry
>
> 303 Engel Hall
> 340 West Campus Dr.
> Blacksburg, VA 24061
>
> jalemkul at vt.edu | (540) 231-3129
> http://www.thelemkullab.com
>
> ==================================================
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