Re: [AMBER] Tethering water molecules in the receptor

From: Jason Swails <>
Date: Sat, 4 Oct 2014 23:50:54 -0400

On Oct 4, 2014, at 7:14 PM, George Tzotzos <> wrote:

> Thank you Jason,
> In my simulations I’ve prepared a topology file which includes a water molecule that is deemed to be conserved. In some simulations ( > 60ns) I find that the water molecule diffuses out of the binding pocket.

Well it’s not unusual for “bound” water to exchange with bulk solvent. If you’re running into an issue where the water binding pocket “collapses” after the water escapes and prevents another water from entering, then I can see three possibilities.

1. Water really _doesn’t_ bind there that tightly at the simulated conditions (perhaps it does when crystallized, but not in bulk solution).

2. The force field is insufficient to characterize that interaction “correctly”, and falsely suggests that water does not bind there.

3. The starting conformation is strained such that it forces the water out of the pocket early in the simulation and then collapses the system into an unphysical conformation that does not happen to allow water to access the binding pocket easily.

You can use a distance restraint to make sure that the water does not stray *too* far from the binding pocket, which can be used to correct for known force field deficiencies or to conserve that feature while you carefully equilibrate your system.

If you suspect (2) to be the culprit and decide to add a restraint potential to conserve the water binding behavior, you have to take care that you actually get more information out of the simulation than you put into it.

I hope this helps,

Jason M. Swails
Rutgers University
Postdoctoral Researcher
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Received on Sat Oct 04 2014 - 21:00:02 PDT
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