Dear Prof. Cheatham,
Thank you very much for ur reply. Now I got more idea about MD.
Also one more doubt, how can I make sure that the system reached
equilibration? My systems contains 437 res and 14500 water molecules.
When I checked the density of the system its close to 0.99 or 0.98
always.. So I thought it equilibrated very well..If the system doesnt
reach the equlibration stage, how can I know that....?
Is 2ns equilibration is sufficient..?
Now I m going to do a number of simulations taking into account ur
suggestions....
I will consider these changes as u mentioned.. taup = 0.2 for
equlibration, cut=9A and forcefield changes....
" [Instabilities could also result from the force field; I would
>suggest
> ff99SB + parmbsc0 for the protein-DNA]. "
can use SO Can I use FF10 forcefield? I have seen from Amber 11 manual
that FF10 includes both of these...
Thank you very much for ur reply...
Thanks
On Fri, 8 Jul 2011 15:49:34 -0600 (Mountain Daylight Time)
Thomas Cheatham III <tec3.utah.edu> wrote:
>
> Re: http://archive.ambermd.org/201107/0123.html
> http://archive.ambermd.org/201107/0093.html
>
> Note that if people do not reply in a timely manner, please do not
>simply
> repost older messages. Try re-phrasing / condensing and/or make it
> clear that you are asking again since you did not get sufficient
>help
> previously.
>
>> I am working on DNA-protein interactions. I have followed the
>> following steps:
> ...
>> I have performed 9 (A-I) different simulations with different
>> temperature coupling parameter (gamma_ln ) and pressure couling
> ...
>> I calculated the RMSD deviations withrest to the first frame (BLACK
>> lines in the RMSD plots) in the production stage and also with
>>repect
>> to the minimized structure after minimzation step2 (RED lines).. I
>> have attached the RMSD plots. The RMSD plots shows a large variation
>> upon changing the simulation parameters..?
> ...
>> If these trajectories differ by changing the simulations parameters,
>> how we can trust these results?
>
> MD simulations are chaotic and small changes in parameters or
>initial
> conditions (and/or parallelism) will lead to different results. As
> pointed out by Professor Roitberg, a key question is whether the
>observed
> differences are expected and/or statistically significant.
>
> Before assuming that the differences observed are real, convince
>yourself
> that they are statistically significant. Roitberg suggested that
>you
> cannot easily compare results from different runtime parameters
>(i.e.
> gamma_ln); you replied that perhaps that meant you should re-run all
>the
> simulations (to which no one replied).
>
> Since you have set ig=-1, re-running should lead to different
>results
> (noting that you may want to set ig=-1 in the heat1 phase).
> However, you
> need not re-run all of them. Pick one set of conditions (gamma_ln,
>taup,
> dt) and run these simulations multiple times. What you likely will
> observe is similar differences to what you saw previously under
>multiple
> conditions, i.e. that the system has not converged and the results
>vary
> considerably from simulation to simulation (although I could be
>wrong
> here). Another good way to get different initial conditions is to
>use a
> different ion distribution (you can use randomizeions in ptraj).
>
>> Is there any 'best parameters for gamma_ln and taup.
>
> The less often you perturb the temperature, the better, however I
>would
> not expect significant differences in the results for simulations
>with
> gamma_ln = 1 or 2 or 3. For equilibration, I set taup smaller (0.2
>or
> 1.0) to get the pressure correct quickly, and then during production
> either run constant volume or set taup larger (5.0, 10.0) for less
> perturbation.
>
>> Is there any problems in the MD protocol which I followed?
>
> The protocol is (mostly) fine; likely the observed differences are
>not
> statistically significant.
>
>> What is the reason for the odd behaviour in the RMSD plots and what
>> should I do to get a stable MD trajectory?
>
> A subtlety relates to the restraints on the protein+DNA with
>constant
> pressure since the positions of the molecules are scaled shifting
>the
> relative positions of the molecules as the simulation runs. If the
>box
> size changes significantly (it shrinks by default with standard LEaP
> solvateOct/solvateBox), this can lead to the molecules getting
>closer
> together despite the restraints. To get around this, the molecules
>have
> to be merged into a single molecule which requires hacking the
>prmtop.
>
> http://archive.ambermd.org/200609/0171.html
>
> If this molecule shifting is leading to instability (i.e. the
>structural
> distortion you are seeing), you can try turning off the restraints
>or use
> only positionally independent restraints (like h-bonds) on the
>initial
> structures. Or only restrain one of the molecules (i.e. protein).
>
> Now, looking at the RMSd plots, we must wonder if differences of 1-3
> Angstrom are significant? Atoms have net thermal motion so we
>expect some
> RMSd; also, the more atoms, the larger the RMSd will be. To check
>this
> out you need to look at average structures and compare them from the
> different simulations. I suggest creating average structures from
>3-4ns
> and comparing them. You may also consider looking at 2D-RMS plots
>(either
> across an individual trajectory or all pooled together to show
> similarities).
>
>Finally, as pointed out by Dan Roe, 4 ns is clearly not sufficient to
> relax the protein, DNA, solvent and ion environment. This may
>require
> longer...
>
> Note also:
>
>> Heating Stage 1
>> &cntrl
>> cut = 12.0,
>> /
>
> The cutoff is rather large for an explicit water simulation with
>PME; I
> would suggest 8.0 or 9.0 angstroms, but first convince yourself that
>the
> small differences in the results between modest changes in time step
>or
> Langevin coupling are real.
>
> [Instabilities could also result from the force field; I would
>suggest
> ff99SB + parmbsc0 for the protein-DNA].
>
> --tec3
>
>
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Received on Fri Jul 08 2011 - 16:00:03 PDT
