Hi,
You may also want to try the system preparation protocol outlined
here: https://aip.scitation.org/doi/abs/10.1063/5.0013849
-Dan
On Tue, Nov 24, 2020 at 7:41 AM Carlos Simmerling
<carlos.simmerling.gmail.com> wrote:
>
> it's quite different equilibration from what we used. I don't know if the
> problems you are seeing are due to that, but since the 2v1b works and 2v1a
> does not, it suggests that it might be due to equilibration. When using
> 2v1a as the initial structure, you are far from equilibrium at the start
> and need to slowly adjust to introducing the new bond and adjusting to new
> geometries in the flavin, etc. In my experience the GPU code can run into
> trouble if the system is at all unstable. You might try tracking your
> energies and other properties from the mdout files and see if they have
> reached a plateau before going to the next step, your MD stages are fairly
> short.
> Here is what we used that worked well for us:
>
> Minimization and equilibration were carried out using Amber version
> 16.(39,40) Initial minimization was performed for 100 000 steps with
> restraints on all atoms except hydrogens, water, C450, and the flavin. The
> restraint force constant was 100 kcal·mol–1·Å–2. Next, the system was
> heated from 100 to 298 K over 1 ns in the NVT ensemble, with a time step of
> 1 fs and SHAKE on all bonds including hydrogen. A nonbonded cutoff of 8 Å
> was used, with long-range electrostatics included by the particle mesh
> Ewald method.(41) The same restraints were maintained. Temperature was
> maintained using a Langevin thermostat with γ set to 1.0. Next, pressure
> and density were relaxed using 1 ns NPT simulation at 298 K with a strong
> pressure coupling constant of 0.1 and all other parameters maintained from
> the prior step. Next, 1 ns MD was performed using the same protocol but
> with restraint force constant reduced to 10.0 and pressure coupling
> constant increased to 0.5. Next, minimization was performed for 10000 steps
> after removing all restraints except those on protein backbone CA, N, and C
> atoms, and no restraints on C450. Next, 1 ns MD in the NPT ensemble at 298
> K was performed using the same protocol as above, with restraints only on
> backbone CA, N, and C atoms excepting C450. The restraint force constant
> was then reduced from 10.0 to 1.0 and an additional 1 ns MD was carried
> out, followed by 1 ns MD with restraint force constant reduced to 0.1.
> Finally, 1 ns of fully unrestrained MD was performed with NPT at 298 K.
>
> On Tue, Nov 24, 2020 at 6:44 AM Amit Sharma (Asstt. Prof., MCARS) <
> asharma4.jmi.ac.in> wrote:
>
> > I tried simulation using 2v1b (crystal structure in photoexcited state). It
> > works fine in that case and is currently running at 2 micro second.
> >
> > My equilibration protocol is as follows
> >
> > 1. 3000 cycle minimization under 100 kcal mol-1 A-2 restraint on the
> > protein
> > 2. 5000 cycle minimization under 25 kcal mol-1 A-2 restraint on the protein
> > 3. 100000 cycle minimization without any restraints
> > 4. 20ps md at nvt where system was heated from 0 to 300K, with 10 kcal
> > mol-1 A-2 restraint on the protein, 2fs time step by keeping SHAKE on. cut
> > of 10 A
> > 5. 80ps md at nvt at 300 K, with 0.5 kcal mol-1 A-2 restraint on the
> > protein, 2fs time step by keeping SHAKE on. cut of 10 A
> >
> > System remains fine until step 5, but blows when I start (using gpu) ntp
> > (ntb = 2, pressure 1atm, ntp = 1) at 300K.
> >
> >
> > When doing the same using cpu, it seems fine at least for initial 100ps.
> > But, issue is that I cannot go on cpu for the simulation where a few micro
> > second run is needed before we could actually see J alpha unfolding.
> >
> > In your paper you retain the crystallographic water and use four point opc
> > water. But, what I am using is tip3p. Can that make a difference?
> >
> > Amit
> >
> >
> > On Tue, Nov 24, 2020 at 4:40 PM Carlos Simmerling <
> > carlos.simmerling.gmail.com> wrote:
> >
> > > Have you tried the simulation without adding the adduct? Also you didn't
> > > describe your equilibration protocol. I believe the one we used should be
> > > described in our paper on that system. Dan Roe also has a nice paper on
> > > equilibration.
> > > Carlos
> > >
> > > On Tue, Nov 24, 2020, 6:05 AM Amit Sharma (Asstt. Prof., MCARS) <
> > > asharma4.jmi.ac.in> wrote:
> > >
> > > > Hi,
> > > >
> > > > I trying to simulate protein having of FMN Cys adduct.
> > > >
> > > > When running md using nvt and positional restraints of 0.5 kcal mol-1
> > A-2
> > > > on the protein, the system remains fine.
> > > >
> > > > But as I switch to npt and remove all the restraints system blows up
> > and
> > > > water molecules start flying away.
> > > >
> > > > Error message is as follows:
> > > >
> > > > "ERROR: Calculation halted. Periodic box dimensions have changed too
> > > much
> > > > from their initial values.
> > > > Your system density has likely changed by a large amount, probably
> > from
> > > > starting the simulation from a structure a long way from equilibrium.
> > > >
> > > > [Although this error can also occur if the simulation has blown up
> > for
> > > > some reason]
> > > >
> > > > The GPU code does not automatically reorganize grid cells and thus
> > you
> > > > will need to restart the calculation from the previous restart file.
> > > > This will generate new grid cells and allow the calculation to
> > > continue.
> > > > It may be necessary to repeat this restarting multiple times if your
> > > > system
> > > > is a long way from an equilibrated density.
> > > >
> > > > Alternatively you can run with the CPU code until the density has
> > > > converged
> > > > and then switch back to the GPU code."
> > > >
> > > > Can anyone suggest how to deal with this?
> > > >
> > > > Thank You,
> > > >
> > > > Amit
> > > >
> > > > --
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Received on Wed Nov 25 2020 - 07:30:03 PST
