Simple: use two separate NMR restraints. Sample both of them
thoroughly--there must be a two dimensional grid of windows with
overlapping sampling in both dimensions. Then, submit all of the results
to Alan Grossfield's WHAM program, in much the same way as you'd do
one-dimensional umbrella sampling. The complexity with two-dimensional
WHAM / Umbrella sampling is not on the MD side (you just need to run more
windows), it's on the analysis side, but fortunately Alan has thought all
that out.
http://membrane.urmc.rochester.edu/content/wham
Same as with one dimensional sampling, there could be rare events that
throw a switch in the track as you count down the umbrellas, so use your
better judgment. For instance, if you are doing one dimensional sampling
of a ligand binding to a basket-shaped clip molecule starting from far out
in solution, there is a critical phase of the sampling where the ligand is
restrained to a distance that would put it just at the entrance of the
basket molecule, at which point it will either continue to enter or flip to
the side and thereafter get pulled harder and harder against the wall from
outside the basket. Umbrella sampling will not work in this case if the
series of umbrellas never shows the molecule entering the basket. With two
dimensional sampling, you could fix the ligand position relative to a point
in the interior of the basket as well as to a second point at the opening
of the basket, and iteratively adjust both restraints so that the ligand's
path is practically guaranteed to take it into the basket. This might be
what you want to study, but in doing so the binding energy might be
over-estimated by the deliberate choice of an umbrella series that always
led the ligand into the basket and neglected outcomes where the ligand
missed or bound weakly to the outside.
The point is that you can, deliberately or not, still have issues with your
umbrella sampling, and therefore it is important to recognize high barriers
on the energy surface and make sure that your sampling has plenty of
opportunities to choose either side of them. A good diagnostic is to look
at your final PMF plot, trace the series of umbrellas on that PMF, and then
decide if barriers in the umbrella series may have played a role in the
contours that you see.
Dave
On Wed, Jun 8, 2016 at 12:16 AM, Airy Sanjeev <airy.sanjeev01.gmail.com>
wrote:
> Dear Amber Users,
> I wanted to do umbrella sampling with two degrees of freedom for a
> dimer system. How to proceed?
> One being the distance between the monomeric units in the dimer and
> the other one is angle along the axes between the monomeric units.
>
> Thanks in advance
>
> --
> with best regards,
> Airy Sanjeev
> Research Scholar
> Dept. of MBBT
> Tezpur University
> Napaam,Tezpur-784028
> Sonitpur,Assam
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
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Received on Tue Jun 07 2016 - 22:00:03 PDT
