[gmx-users] REMD - replicas sampling in temperatures beyond the assigned range

NISHA Prakash nishnith20591 at gmail.com
Thu Jun 30 16:15:42 CEST 2016


Dear Justin,

Thanks a lot for pointing out the issues. I now understand why there were
such high oscillations.

Could you please also tell me if there are any ideal values for pme_order
and fourier spacing with respect to the cut offs' value of 1.4.

Does the following Note imply I can raise the fourier grid spacing to 0.25?

NOTE 2 [file sim-new.mdp]:
  The optimal PME mesh load for parallel simulations is below 0.5
  and for highly parallel simulations between 0.25 and 0.33,
  for higher performance, increase the cut-off and the PME grid spacing

Thank you again,

Nisha


On Thu, Jun 30, 2016 at 6:55 PM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 6/30/16 9:16 AM, NISHA Prakash wrote:
>
>> Dear Justin,
>>
>> Thank you for your reply.
>> It is a protein carbohydrate system.  Including the solvent, the number of
>> atoms is 43499.
>> I have minimized the system for 200 ps followed by NPT and NVT simulations
>> for 200 ps respectively
>>
>>
> Given that your temperature output started from 0 K, then you did not
> continue from the equilibration properly by supplying the checkpoint file
> to grompp -t. This is important to get right, otherwise you're basically
> starting over from some random point (an equilibrated structure without any
> velocities likely isn't a physically realistic state).
>
> Below is the .mdp file.
>>
>>
>> ; VARIOUS PREPROCESSING OPTIONS
>> title                    = REMD Simulation
>> define                   = -DPOSRES
>>
>>
>> ; RUN CONTROL PARAMETERS
>> integrator               = md-vv  ; velocity verlet algorithm -
>> tinit                    = 0 ;
>> dt                       = 0.002    ; timestep in ps
>> nsteps              = 5000000    ;
>> simulation-part          = 1 ; Part index is updated automatically on
>> checkpointing
>> comm-mode                = Linear ; mode for center of mass motion removal
>> nstcomm                  = 100 ; number of steps for center of mass motion
>> removal
>> comm-grps                = Protein_Carb      Water_and_Ions ; group(s) for
>> center of mass motion removal
>>
>>
> In a solvated system, you should not be separating these groups.  This
> could explain the sudden jump in temperature - you could have things
> clashing badly over the course of the simulation.
>
>
>
>> ; ENERGY MINIMIZATION OPTIONS
>> emtol                    = 10 ; Force tolerance
>> emstep                   = 0.01 ; initial step-size
>> niter                    = 20 ; Max number of iterations in relax-shells
>> fcstep                   = 0 ; Step size (ps^2) for minimization of
>> flexible constraints
>> nstcgsteep               = 1000 ; Frequency of steepest descents steps
>> when
>> doing CG
>> nbfgscorr                = 10
>>
>>
>> ; OUTPUT CONTROL OPTIONS
>> nstxout                  = 50000 ; Writing full precision coordinates
>> every
>> ns
>> nstvout                  = 50000 ; Writing velocities every nanosecond
>> nstfout                  = 0     ; Not writing forces
>> nstlog                   = 5000  ; Writing to the log file every step 10ps
>> nstcalcenergy            = 100
>> nstenergy                = 5000  ; Writing out energy information every
>> step 10ps
>> nstxtcout                = 2500  ; Writing coordinates every 5 ps
>> xtc-precision            = 1000
>> xtc-grps                 = Protein_Carb      Water_and_Ions ; subset of
>> atoms for the .xtc file.
>> energygrps               = Protein_Carb      Water_and_Ions ; Selection of
>> energy groups
>>
>>
>> ; NEIGHBORSEARCHING PARAMETERS
>> nstlist                  = 10     ; nblist update frequency-
>> ns-type                  = Grid     ; ns algorithm (simple or grid)
>> pbc                      = xyz     ; Periodic boundary conditions: xyz,
>> no,
>> xy
>> periodic-molecules       = no
>> rlist                    = 1.4     ;  nblist cut-off
>> rlistlong                = -1     ; long-range cut-off for switched
>> potentials
>>
>>
>> ; OPTIONS FOR ELECTROSTATICS
>> coulombtype              = PME ; Method for doing electrostatics
>> rcoulomb                 = 1.4 ;
>> epsilon-r                = 1     ; Relative dielectric constant for the
>> medium
>> pme_order                = 10;
>>
>>
>> ; OPTIONS FOR VDW
>> vdw-type                 = Cut-off      ; Method for doing Van der Waals
>> rvdw-switch              = 0     ; cut-off lengths
>> rvdw                     = 1.4 ;
>> DispCorr                 = EnerPres; Apply long range dispersion
>> corrections for Energy and Pressure
>> table-extension          = 1    ; Extension of the potential lookup tables
>> beyond the cut-off
>> fourierspacing           = 0.08    ;  Spacing for the PME/PPPM FFT grid
>>
>>
> This small Fourier spacing, coupled with the very high PME order above, is
> going to unnecessarily slow your system down.  Is there some reason you
> have set these this way?
>
>
>> ; GENERALIZED BORN ELECTROSTATICS
>> gb-algorithm             = Still    ; Algorithm for calculating Born radii
>> nstgbradii               = 1    ; Frequency of calculating the Born radii
>> inside rlist
>> rgbradii                 = 1    ; Cutoff for Born radii calculation
>> gb-epsilon-solvent       = 80    ; Dielectric coefficient of the implicit
>> solvent
>> gb-saltconc              = 0    ; Salt concentration in M for Generalized
>> Born models
>>
>>
>> ; Scaling factors used in the OBC GB model. Default values are OBC(II)
>> gb-obc-alpha             = 1
>> gb-obc-beta              = 0.8
>> gb-obc-gamma             = 4.85
>> gb-dielectric-offset     = 0.009
>> sa-algorithm             = Ace-approximation
>> sa-surface-tension       = -1    ; Surface tension (kJ/mol/nm^2) for the
>> SA
>> (nonpolar surface) part of GBSA - default -1
>>
>>
> Implicit solvent should not be used if you have explicit solvent, though
> it looks like these options are probably off since the default for the
> implicit-solvent keyword is "no," but be aware that these are extraneous.
>
>
>>
>> ; Temperature coupling
>> tcoupl             = nose-hoover
>> nsttcouple               = 10 ;
>> nh-chain-length          = 10
>> tc-grps                  = Protein_Carb      Water_and_Ions ; Groups to
>> couple separately
>> tau-t                    = 10    10; Time constant (ps)-
>>
>
> tau-t = 10 is far too permissive and will allow the temperature to
> oscillate very widely.  A value of 1 or so should generally be used with
> N-H.
>
> -Justin
>
>
> ref-t              = 270.0     270.0; reference temperature (K)
>>
>>
>> ; pressure coupling
>> pcoupl                   = no  ;-
>>
>>
>> ; GENERATE VELOCITIES FOR STARTUP RUN
>> gen-vel          = no
>> gen-temp          = 270.0
>> gen-seed                 = 173529
>>
>>
>> ; OPTIONS FOR BONDS
>> continuation         = yes     ;  constrain the start configuration
>>
>> constraints              = all-bonds
>> constraint-algorithm     = lincs     ; Type of constraint algorithm-
>> lincs-order              = 4
>> lincs-iter               = 1
>> lincs-warnangle          = 30
>>
>>
>> Thank you for your help.
>>
>> Nisha
>>
>>
>>
>> On Thu, Jun 30, 2016 at 6:21 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>
>>
>>>
>>> On 6/30/16 8:46 AM, NISHA Prakash wrote:
>>>
>>> Dear all,
>>>>
>>>> I have conducted a 10ns REMD simulation for a protein ligand complex
>>>> with
>>>> the temperature range - 270 to 350 K, however the temperature
>>>> distribution
>>>> plot of the replicas show that the sampling has occurred at higher
>>>> temperatures as well that is beyond 350K -
>>>> Below is an excerpt from the temperature xvg file
>>>>
>>>>
>>>> @    title "Gromacs Energies"
>>>> @    xaxis  label "Time (ps)"
>>>> @    yaxis  label "(K)"
>>>> @TYPE xy
>>>> @ view 0.15, 0.15, 0.75, 0.85
>>>> @ legend on
>>>> @ legend box on
>>>> @ legend loctype view
>>>> @ legend 0.78, 0.8
>>>> @ legend length 2
>>>> @ s0 legend "Temperature"
>>>>     0.000000    0.000000
>>>>    10.000000  350.997864
>>>>    20.000000  353.618927
>>>>    30.000000  350.068481
>>>>    40.000000  353.921753
>>>>    50.000000  359.485565
>>>>    60.000000  353.463654
>>>>    70.000000  352.015778
>>>>    80.000000  350.657898
>>>>    90.000000  351.927155
>>>>   100.000000  354.539429
>>>>   110.000000  354.287720
>>>>   120.000000  349.436096
>>>>   130.000000  352.960541
>>>>   140.000000  351.631317
>>>>   150.000000  354.217407
>>>>   160.000000  350.185852
>>>>   170.000000  350.294434
>>>>   180.000000  350.980194
>>>>   190.000000  350.914429
>>>>                    ....
>>>>                    ....
>>>>  470.000000  349.224060
>>>>   480.000000  350.819458
>>>>   490.000000  348.541748
>>>>   500.000000  350.393127
>>>>   510.000000  398.775208
>>>>   520.000000  444.802856
>>>>   530.000000  470.899323
>>>>   540.000000  466.652740
>>>>   550.000000  465.600677
>>>>   560.000000  469.225555
>>>>   570.000000  470.548370
>>>>   580.000000  470.011566
>>>>   590.000000  470.643951
>>>>   600.000000  472.433197
>>>>   610.000000  470.451172
>>>>   620.000000  469.991699
>>>>   630.000000  469.073090
>>>>   640.000000  467.259521
>>>>   650.000000  464.561798
>>>>   660.000000  468.416901
>>>>   670.000000  468.754913
>>>>   680.000000  469.259613
>>>>   690.000000  467.641144
>>>>   700.000000  468.542328
>>>>
>>>>
>>>> Temperature coupling was done using Nose hoover algorithm.
>>>>
>>>> Does this imply the sampling is wrong or insufficent?
>>>> Any help / suggestion is appreciated.
>>>>
>>>>
>>>> How large is your system, and what is it?  What were your (full) .mdp
>>> settings? The fact that your temperature started at 0 K and ramped up
>>> suggests that you did not equilibrate prior to the run, did not generate
>>> appropriate velocities, or did not continue properly.  The sudden jump in
>>> temperature later suggests instability, and could be due to incorrect
>>> settings.  N-H allows for large oscillations, but I wouldn't expect a
>>> stable system to that degree.
>>>
>>> -Justin
>>>
>>> --
>>> ==================================================
>>>
>>> Justin A. Lemkul, Ph.D.
>>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>>>
>>> Department of Pharmaceutical Sciences
>>> School of Pharmacy
>>> Health Sciences Facility II, Room 629
>>> University of Maryland, Baltimore
>>> 20 Penn St.
>>> Baltimore, MD 21201
>>>
>>> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
>>> http://mackerell.umaryland.edu/~jalemkul
>>>
>>> ==================================================
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>>>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==================================================
> --
> Gromacs Users mailing list
>
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