[gmx-users] Re: free energy calculation , grompp crash

Da-Wei Li lidawei at gmail.com
Mon Feb 7 19:38:13 CET 2011


hello

My goal is to study the solvation free energy of a fixed protein and compare
it with implicit model. The pr1. mdp is just a test case. Grompp always need
more than 10 minutes to finish for my 76 residues protein when free_energy =
yes, no matter there is PR or not, whether I switch off only vdm or switch
both ele and vdm.

The memory usage is <1% on a system with 16GB memory so that memory
limitation can be ruled out.

best,

dawei



On Mon, Feb 7, 2011 at 1:31 PM, TJ Mustard <mustardt at onid.orst.edu> wrote:

>  Da-Wei,
>
>
>  Do you need FEP information on the PR step? Are you going to do a MD(sd)
> with FEP on after the PR?
>
>
>
> And are you doing hydration of a protein?
>
>
>
> Thank you,
>
> TJ Mustard
>  On February 7, 2011 at 10:23 AM "Justin A. Lemkul" <jalemkul at vt.edu>
> wrote:
>
> >
> >
> > Da-Wei Li wrote:
> > > hello
> > >
> > > Here they are the command line and mdp file. I use Gromacs 4.5.3. This
> > > is a test case only and the protein is 1UBQ. Grompp wills top for about
> > > 10 minutes then go through.
> > >
> >
> > The efficiency of this kind of process will depend on the amount of
> available
> > memory on the system.  You're asking grompp to decouple a huge amount of
> degrees
> > of freedom, which will require a lot of memory to do.  It sounds like
> it's
> > working, in any case, so there's no real problem.
> >
> > Whether or not simultaneously decoupling the LJ and Coulombic
> interactions of a
> > whole protein will generate a stable trajectory or sensible result is
> another
> > matter.
> >
> > -Justin
> >
> > > ***********output of grompp*****************
> > >
> > > Back Off! I just backed up mdout.mdp to ./#mdout.mdp.6#
> > > Generated 2278 of the 2278 non-bonded parameter combinations
> > > Generating 1-4 interactions: fudge = 0.5
> > > Generated 2278 of the 2278 1-4 parameter combinations
> > > Excluding 3 bonded neighbours molecule type 'Protein'
> > > turning H bonds into constraints...
> > > Excluding 2 bonded neighbours molecule type 'SOL'
> > > turning H bonds into constraints...
> > > Coupling 1 copies of molecule type 'Protein'
> > > Setting gen_seed to 8552
> > > Velocities were taken from a Maxwell distribution at 300 K
> > > ********************************
> > >
> > > Command line and mdp file:
> > >
> > > ******************************
> > > grompp -f pr1.mdp -c after_em.gro -t em.trr -p topol.top -o pr1
> > > ******************************
> > > define = -DPOSRES ; position restrain the protein
> > > ; Run parameters
> > > integrator = sd ; leap-frog integrator
> > > nsteps = 5000 ; 2 * 50000 = 100 ps
> > > dt = 0.002 ; 2 fs
> > > ; Output control
> > > nstxout = 1000 ; save coordinates every 2 ps
> > > nstvout = 5000 ; save velocities every 100ps
> > > nstenergy = 1000 ; save energies every 2 ps
> > > nstlog = 1000 ; update log file every 2 ps
> > > ; Bond parameters
> > > continuation = no ; first dynamics run
> > > constraint_algorithm = lincs ; holonomic constraints
> > > constraints = hbonds ; 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 = 10 ; 20 fs
> > > rlist = 0.8 ; short-range neighborlist cutoff (in nm)
> > > rcoulomb = 0.8 ; short-range electrostatic cutoff (in nm)
> > > rvdw = 1.0 ; short-range van der Waals cutoff (in nm)
> > > ; Electrostatics
> > > coulombtype = PME ; Particle Mesh Ewald for long-range electrostatics
> > > pme_order = 4 ; cubic interpolation
> > > fourierspacing = 0.12 ; grid spacing for FFT
> > > ; Temperature coupling is on
> > > tcoupl = V-rescale ; modified Berendsen thermostat
> > > tc-grps = Protein Non-Protein ; two coupling groups - more accurate
> > > tau_t = 0.1 0.1 ; time constant, in ps
> > > ref_t = 300 300 ; reference temperature, one for each group, in K
> > > ; Pressure coupling is off
> > > pcoupl = no ; no pressure coupling in NVT
> > > ; Periodic boundary conditions
> > > pbc = xyz ; 3-D PBC
> > > ; Dispersion correction
> > > DispCorr = EnerPres ; account for cut-off vdW scheme
> > > ; Velocity generation
> > > gen_vel = yes ; assign velocities from Maxwell distribution
> > > gen_temp = 300 ; temperature for Maxwell distribution
> > > gen_seed = -1 ; generate a random seed
> > > ;free energy stuff
> > > free_energy              = yes
> > > init_lambda              = 0.0
> > > delta_lambda             = 0
> > > sc_alpha                 =0.5
> > > sc-power                 =1.0
> > > sc-sigma                 = 0.3
> > > couple-moltype           = Protein
> > > couple-lambda0           = vdw-q
> > > couple-lambda1           = none
> > > *******************************
> > >
> > > thanks.
> > >
> > > dawei
> > >
> > >
> > >
> > >
> > > On Mon, Feb 7, 2011 at 1:05 PM, TJ Mustard <mustardt at onid.orst.edu
> > > <mailto:mustardt at onid.orst.edu>> wrote:
> > >
> > >     Dawei,
> > >
> > >
> > >
> > >     I have no problems with proteins in the thousands of atoms. Can you
> > >     post your command line and mdp files?
> > >
> > >
> > >
> > >     Thank you,
> > >
> > >     TJ Mustard
> > >
> > >
> > >     On February 7, 2011 at 9:31 AM Da-Wei Li <lidawei at gmail.com
> > >     <mailto:lidawei at gmail.com>> wrote:
> > >
> > >>     Well. It  actually isn't dead but becomes very slow for large
> > >>     proteins.   dawei
> > >>
> > >>     On Mon, Feb 7, 2011 at 11:44 AM, Da-Wei Li <lidawei at gmail.com
> > >>     <mailto:lidawei at gmail.com>> wrote:
> > >>
> > >>         hi,
> > >>         I did more test and found that it depended on size of the
> > >>         protein. Grompp will die when number of atoms of the protein
> > >>         is larger than about 200. Is it possible the source code limit
> > >>         the size of the protein that can be decoupled?
> > >>         thanks.
> > >>         dawei
> > >>
> > >>
> > >>         On Mon, Feb 7, 2011 at 10:34 AM, Da-Wei Li <lidawei at gmail.com
> > >>         <mailto:lidawei at gmail.com>> wrote:
> > >>
> > >>             Dear users
> > >>             I tried free energy calculation but grompp couldn't go
> > >>             through. It stops after
> > >>             *******************
> > >>             Generated 2278 of the 2278 non-bonded parameter
> combinations
> > >>             Generating 1-4 interactions: fudge = 0.5
> > >>             Generated 2278 of the 2278 1-4 parameter combinations
> > >>             Excluding 3 bonded neighbours molecule type 'Protein'
> > >>             turning H bonds into constraints...
> > >>             Excluding 2 bonded neighbours molecule type 'SOL'
> > >>             turning H bonds into constraints...
> > >>             Excluding 1 bonded neighbours molecule type 'CL'
> > >>             turning H bonds into constraints...
> > >>             Coupling 1 copies of molecule type 'Protein'
> > >>             *******************
> > >>             The CPU usage is 100%.
> > >>             I just add following into the mdp file:
> > >>             ***************
> > >>             free_energy              = yes
> > >>             init_lambda              = 0.0
> > >>             delta_lambda             = 0
> > >>             sc_alpha                 =0.5
> > >>             sc-power                 =1.0
> > >>             sc-sigma                 = 0.3
> > >>             couple-moltype           = Protein
> > >>             couple-lambda0           = vdw-q
> > >>             couple-lambda1           = none
> > >>             ***************
> > >>             Does anyone have some idea about this problem?  thanks.
> > >>             Another question is whether I can switch off "two
> > >>             molecules" (such as protein+ligand) in free energy
> > >>             calculation? I searched this list and got that 4.0.7 did
> > >>             support this. how about 4.5.4?
> > >>             dawei
> > >>
> > >>
> > >
> > >
> > >     TJ Mustard
> > >     Email: mustardt at onid.orst.edu <mailto:mustardt at onid.orst.edu>
> > >
> > >
> > >     --
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> > >
> >
> > --
> > ========================================
> >
> > Justin A. Lemkul
> > Ph.D. Candidate
> > ICTAS Doctoral Scholar
> > MILES-IGERT Trainee
> > Department of Biochemistry
> > Virginia Tech
> > Blacksburg, VA
> > jalemkul[at]vt.edu | (540) 231-9080
> > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> >
> > ========================================
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>
>
>
> TJ Mustard
> Email: mustardt at onid.orst.edu
>
> --
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