Re: [AMBER] Drifting molecules despite strong restraints

From: Jason Swails <>
Date: Fri, 20 Mar 2015 08:22:03 -0400

On Thu, Mar 19, 2015 at 6:32 PM, Sanmeet Chahal <> wrote:

> Hello all,
> I am trying to run a simulation with two of the molecules being restrained
> to their original positions. However after I visualize the trajectory with
> VMD, the restrained molecules show a drift from their current position over
> time.
> The prmtop, inpcrd, and in files can be found here:
> My procedure is the following:
> 1) minimize, 2) heat at NPT conditions
> Here are the commands I used :
> sander -O -i -o min-file.out -p file.prmtop -c file.inpcrd \
> -r min-file.rst -inf min-file.mdinfo -ref file.inpcrd
> sander -O -i -o heat-file.out -p file.prmtop -c min-file.rst -r
> heat-file.rst \
> -x heat-file.mdcrd -inf heat-file.mdinfo -ref file.inpcrd
> I have found that someone was having similar issues before:

​I see a number of unrelated issues with your input file:

You set ntc=2 to turn on shake, but then set ntf=7 to prevent any bond,
angle, or dihedral forces from being calculated (!!) This will most likely
render your simulation results meaningless​. So you should set ntf=2 (with
ntc=2) unless you *know* what you're doing and wanted to see nonbonded-only
dynamics for whatever reason.

Also, you are running constant pressure simulations when your temperature
is initially 0 K. This can cause weird behavior. My suggestion is to heat
up at constant volume rather quickly (over 10 to 100 ps), then switch to
constant pressure in order to equilibrate density.

​Finally, your restraint weight is *incredibly* large. I would suggest a
value one to two orders of magnitude smaller. (A value of 20 will
definitely keep your first two residues fixed in place, without introducing
overly high vibrational frequencies).​

​Also, nsnb is ​really no longer useful. It's ignored for MD, and
generally unnecessary for minimizations. I would suggest removing
variables from the input file that you're not using, or that you are just
setting to their default value. Same goes for ew_type -- there is *very*
rarely an instance where you would want to do an Ewald calculation
(ew_type=1) rather than a PME calculation (ew_type=0, default).

I attempted to use the suggestion by setting nscm to be larger than nstlim
> but this problem still persists.

​One thing that I know happens when you use restraints with constant
pressure simulations is that the reference coordinates are "scaled" with
the regular coordinates when the box grows or shrinks (in order to
accommodate the effect of the external pressure). This is a *good* thing,
but as the box "breathes" it can give the appearance of restrained atoms
'drifting' during the simulation.

You can see if this is the actual cause by running a NVT simulation during
your heating stage instead and making sure that the effect goes away.


Jason M. Swails
Rutgers University
Postdoctoral Researcher
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Received on Fri Mar 20 2015 - 05:30:07 PDT
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