Thank you Justin.
On Wed, Jun 27, 2012 at 2:39 PM, Justin A. Lemkul <jalem...@vt.edu> wrote: > > > On 6/27/12 9:36 AM, Steven Neumann wrote: >> >> On Wed, Jun 27, 2012 at 1:51 PM, Justin A. Lemkul <jalem...@vt.edu> wrote: >>> >>> >>> >>> On 6/27/12 7:48 AM, Steven Neumann wrote: >>>> >>>> >>>> Dear Gmx Users, >>>> >>>> I obtained a protein-ligand complex from 100ns simulation. Now I am >>>> pulling my ligand away from the protein after the energy minimzation >>>> in water and equilibration of 100ps (two coupling baths: Protein, >>>> LIG_Water_and_ions). >>>> Then I proceed my pulling : >>>> >>>> grompp -f pull.mdp -c npt.gro -p topol.top -n index.ndx -t npt.cpt -o >>>> pull.tpr >>>> >>>> mdrun -s pull.tpr -deffnm pull >>>> >>>> >>>> title = Umbrella pulling simulation >>>> define = -DPOSRES >>>> ; Run parameters >>>> integrator = md >>>> dt = 0.002 >>>> tinit = 0 >>>> nsteps = 500000 ; 1 ns >>>> nstcomm = 10 >>>> ; Output parameters >>>> nstxout = 0 >>>> nstvout = 0 >>>> nstfout = 500 >>>> nstxtcout = 1000 ; every 1 ps >>>> nstenergy = 500 >>>> ; Bond parameters >>>> constraint_algorithm = lincs >>>> constraints = all-bonds >>>> continuation = yes ; continuing from NPT >>>> ; Single-range cutoff scheme >>>> nstlist = 5 >>>> ns_type = grid >>>> rlist = 1.4 >>>> rcoulomb = 1.4 >>>> rvdw = 1.2 >>>> vdwtype = Switch >>>> rvdw-switch = 1.0 >>>> ; PME electrostatics parameters >>>> coulombtype = PME >>>> fourierspacing = 0.12 >>>> fourier_nx = 0 >>>> fourier_ny = 0 >>>> fourier_nz = 0 >>>> pme_order = 4 >>>> ewald_rtol = 1e-5 >>>> optimize_fft = yes >>>> ; Temperature coupling is on >>>> tcoupl = V-rescale ; modified >>>> Berendsen thermostat >>>> tc_grps = Protein LIG_Water_and_ions ; two coupling groups - more >>>> accurate >>>> tau_t = 0.1 0.1 ; time constant, >>>> in ps >>>> ref_t = 298 298 ; reference >>>> temperature, one for each group, in K >>>> ; Pressure coupling is on >>>> Pcoupl = Parrinello-Rahman >>>> pcoupltype = isotropic >>>> tau_p = 2.0 >>>> compressibility = 4.5e-5 >>>> ref_p = 1.0 >>>> ; Generate velocities is off >>>> gen_vel = no >>>> ; Periodic boundary conditions are on in all directions >>>> pbc = xyz >>>> ; Long-range dispersion correction >>>> DispCorr = EnerPres >>>> ; Pull code >>>> pull = umbrella >>>> pull_geometry = distance ; simple distance increase >>>> pull_dim = N N Y >>>> pull_start = yes ; define initial COM distance > 0 >>>> pull_ngroups = 1 >>>> pull_group0 = Protein >>>> pull_group1 = LIG >>>> pull_rate1 = 0.004 ; 0.004 nm per ps = 4 nm per ns >>>> pull_k1 = 500 ; kJ mol^-1 nm^-2 >>>> >>>> I run 3 pulling simulations with the same mdp and I obtain 3 >>>> different profiles (Force vs time). Then I used 2xlonger pulling with >>>> the same pulling distance and I run 3 simulations again. Each time I >>>> obtain different profile. Can anyone explain me this? I am using >>>> velocities from npt simulation as above (gen_vel = no and continuation >>>> = yes) so I presume the output should be similar. Please, advice. >>>> >>> >>> I assume you're passing a checkpoint file to grompp? If you're relying >>> on >>> velocities from the .gro file, they are of insufficient precision to >>> guarantee proper continuation. >> >> >> Thank you Justin. I am using according to your tutorial: >> >> grompp -f pull.mdp -c npt.gro -p topol.top -n index.ndx -t npt.cpt -o >> pull.tpr >> mdrun -s pull.tpr -deffnm pull >> >> Would you suggest: >> >> grompp -f pull.mdp -c npt.gro -p topol.top -n index.ndx -t npt.cpt -o >> pull.tpr >> mdrun -s pull.tpr -cpi npt.cpt -deffnm pull ?? >> > > No, I would not, especially if the NPT run uses position restraints, in > which case the two phases are different. I missed the command line in the > earlier message. What you are doing makes sense. > > >> Profiles do not vary slightly - the maximum pulling force (breaking >> point) varies from 290 to 500 kJ/mol nm2 which is really a lot. >> > > Consult the points below and watch your trajectories. If you're getting > different forces, your ligands are experiencing different interactions. SMD > is a path-dependent, non-equilibrium process. Good sampling and a > justifiable path are key. > > -Justin > > >>> >>> Small variations are inherent in any simulation set, and in the case of >>> pulling, small changes (though intentional) are the basis for Jarzynski's >>> method. In any case, all MD simulations are chaotic and so it depends on >>> what your definition of "different" is in the context of whether or not >>> there are meaningful changes imparted through the course of each >>> simulation. >>> Also note that in the absence of the -reprod flag, the same .tpr file >>> may >>> result in a slightly different outcome. The implications of these >>> outcomes >>> are limited by sampling; the ensemble should converge with sufficient >>> time >>> and/or replicates. For non-equilibrium processes like pulling, >>> convergence >>> is probably harder, but again you have to ask whether the differences are >>> meaningful. >>> >>> http://www.gromacs.org/Documentation/Terminology/Reproducibility >>> >>> -Justin >>> >>> -- >>> ======================================== >>> >>> Justin A. Lemkul, Ph.D. >>> Research Scientist >>> Department of Biochemistry >>> Virginia Tech >>> Blacksburg, VA >>> jalemkul[at]vt.edu | (540) 231-9080 >>> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin >>> >>> ======================================== >>> >>> >>> -- >>> gmx-users mailing list gmx-users@gromacs.org >>> http://lists.gromacs.org/mailman/listinfo/gmx-users >>> * Only plain text messages are allowed! >>> * Please search the archive at >>> http://www.gromacs.org/Support/Mailing_Lists/Search before posting! >>> * Please don't post (un)subscribe requests to the list. Use the www >>> interface or send it to gmx-users-requ...@gromacs.org. >>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists >> >> > > -- > ======================================== > > Justin A. Lemkul, Ph.D. > Research Scientist > Department of Biochemistry > Virginia Tech > Blacksburg, VA > jalemkul[at]vt.edu | (540) 231-9080 > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin > > ======================================== > > > -- > gmx-users mailing list gmx-users@gromacs.org > http://lists.gromacs.org/mailman/listinfo/gmx-users > * Only plain text messages are allowed! > * Please search the archive at > http://www.gromacs.org/Support/Mailing_Lists/Search before posting! > * Please don't post (un)subscribe requests to the list. Use the www > interface or send it to gmx-users-requ...@gromacs.org. > * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- gmx-users mailing list gmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Only plain text messages are allowed! * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. 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