Re: FEP difficulties between two ion species

From: Niklaus Johner (
Date: Fri May 18 2012 - 09:13:06 CDT

Hi all,

I'm having the same issue with an FEP calculation of the protonation of a sidechain.
My FEP calculations run fine as long as I don't use colvar to add a restraint. If I turn colvar on and add a restraint between an atom from my vanishing sidechain and any atom in my system but the appearing sidechain, it also works fine. But if I add a restraint between atoms from the appearing and vanishing sidechain, then it crashes at the first time step (even if I use forceConstant=0).

It seems that adding a restraint between the vanishing and appearing atoms somehow makes them see each other and clash. Maybe it breaks the automatic generation of the non-bonded exclusion list?

I tried this on namd2.7, namd2.8 and namd2.9.
I haven't tried to use alchemify to create the exclusion list myself yet.

Any input would be welcome.



Niklaus Johner
Weill Cornell Medical College
Harel Weinstein Lab
Department of Physiology and Biophysics
1300 York Avenue, Room D-501
New York, NY 10065

On Apr 24, 2012, at 8:19 AM, Jérôme Hénin wrote:

> Hi Jeremy,
> On 23 April 2012 23:38, Jeremy Parlin <> wrote:
>> I have a system with an ion bound in a protein pocket, with one distance
>> restraint on it set via colvars. I am trying to perform an FEP simulation,
>> where that ion changes species, while the colvar restraint stays applied.
>> I've set this system up, with both ions present in the topology file, having
>> the same initial coordinates, with the old ion set to annihilate and the new
>> one to exnihilate. This executes successfully, however, in the early stages
>> of the simulation, the new ion swims out of the pocket, since it experiences
>> no protein interactions holding it there. To remedy this, I've tried to 'tie
>> together' the two ions. I've tried to do this either with a colvar distance
>> constraint between the two ions (restraining the distance to zero), or by
>> creating a virtual bond in the PSF file (adding a corresponding term to the
>> parameter file). In either case, the simulation fails on the very first
>> step, with both ions having infinite velocity.
> This indicates that something is wrong in the way the simulation is
> set up. The two ions should not interact with each other.
>> Thoughts on how to do this successfully? I'd really like to the exnihilated
>> and annihilated ions to be in effectively the same position as one another
>> at all times, but both to be allowed to fluctuate together within the
>> binding pocket subject to my colvar restraint.
> The strategy you describe is perfectly fine and should yield the
> result you want.
> Now, the problem is probably with your "alchfile" - check that the
> alchemical flags are properly set to -1 and +1 on the two ions, and
> check NAMD's standard output at startup to see if everything is parsed
> as intended. If you can't find the issue, send us a compressed log
> file.
> Last thing: make sure you use a recent version of NAMD, ideally the
> latest, as these things are more automated in recent versions.
> Jerome

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