Re: [AMBER] TI simulations blowing up with clambda = 1 with pmemd

From: Hannes Loeffler <>
Date: Fri, 27 Jan 2017 15:46:01 +0000

On Fri, 27 Jan 2017 14:54:38 +0000
Stefan Ivanov <> wrote:

> Hi Hannes,
> The previous e-mail was too big to post on the mailing list; it
> wouldn't let me.


> Hmmm, the minimization seems to be doing the trick, although there
> aren't any clashes in my starting structures. Also, at lamda = 1 BOTH
> ligands would become completely distorted although at that lambda
> value the template isn't interacting with its environment at all.
> Also, even if there were clashes between the modeled ligand and any
> water molecules and/or ions, it wouldn't cause the whole molecule to
> become completely distorted and keep twisting and deforming
> throughout the whole run, let alone affect the template ligand at
> lambda = 1.

Large parts of your two ligands are single coordinate (or effective
single topology if you like) and you have both appearing and
disappearing parts (softcore). So most of your molecules are present
at all times and single coordinates will distort together.

I have only checked for 20000 steps of heating and 50000 steps of
pressurising. I don't see anything that I would call distorted. One
thought: what if instead of the lib files you have created you directly
load the mol2 files instead and/or update to AmberTools16? BTW, I am
on Amber16.

> I've run 2000 steps of minimization on similar structures and I've
> had similar problems so I'm not sure if this is a general solution or
> works just in this particular case. I'm not really sure what's going
> on here.

I think all you need is a few tens of minimisation. When I set up the
system I had several waters <= 2A near the ligands.

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Received on Fri Jan 27 2017 - 08:00:03 PST
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