[gmx-users] Open-closed transition in a dimeric enzyme, WTM simulations

[tarak karmakar]

Dear Erik,
Thanks for the comment. In my case, the closed state of the enzyme is not
known (no crystal structure). What do you suggest to check for a better
collective variable?
I use two CVs with the information of
1. COM-COM distance between the flexible loop and a core part of the one
subunit
2. local contacts (CMAP description in plumed)

In the simulation trajectories, I see the open-closed transitions several
times. Thus, It is showing the event I am searching for. But I am still
waiting for the converged FES for the same. Currently, I am trying with a
different set of parameters (sigma, hills height).

Regards,
Tarak



On Wed, Jun 15, 2016 at 4:53 PM, Erik Marklund <erik.marklund at chem.ox.ac.uk>
wrote:

> Dear Tarak,
>
> My guess is that your reaction coordinate is ill-chosen and that it fails
> to capture some significant transitions in orthogonal directions. This can
> be difficult to know beforehand unfortunately.
>
> Kind regards,
> Erik
>
> > On 10 Jun 2016, at 19:09, tarak karmakar <tarak20489 at gmail.com> wrote:
> >
> > Dear All,
> > I am studying an enzyme where the closing of a loop should happen upon
> > ligand binding to the active site. In unbiased simulations, even after
> 300
> > ns of simulation time the loop does not close the reaction center. Thus,
> we
> > realized that the open-closed conformational change may have a high free
> > energy barrier, inaccessible by the unbiased trajectory. Thus, we
> performed
> > well-tempered metadynamics (WTM) simulations to study that event.
> >
> > In WTM simulations, we see the opening and closing of the loop almost
> five
> > to six times within 300 ns time span. The free energy associated with
> this
> > event has barriers of only few kJ/mol (almost flat surface). Now, given
> > these low values of the free energy barriers, I would expect to observe
> the
> > open-closed transitions in the unbiased simulations. However, we do not
> see
> > that transition in the unbiased trajectories.
> >
> > So, my questions are,
> > 1) Are the collective variables used here inappropriate? (Although I see
> > the open-closed
> > transition a many times in the metadynamics trajectory.)
> >
> > 2) Is the free energy not converged? (plotting hills heights a function
> of
> > time, decays close to zero after 200-250 ns)
> >
> > 3) How would I make sure that the free energy is converged? (block
> averages
> > using -stride in plumed) How would I decide the blocks from the COLVAR
> plot?
> >
> > Any suggestions would be highly appreciated.
> >
> > --
> > Regards,
> > Tarak
> > --
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-- 
Regards,
Tarak