Re: DOF during alchemical simulations

From: Jérôme Hénin (
Date: Fri Nov 27 2015 - 03:31:25 CST

On 26 November 2015 at 19:28, Aron Broom <> wrote:

> This is really interesting. My knowledge of alchemical transformations in
> limited, but given their successes I'd like to understand more (and will
> happily be corrected on my errors in thinking).
> If you leave those degrees of freedom in, then the end-point simulations
> are actually different than a similar simulation of that system where you
> aren't doing an alchemical transformation. That raises for me a kind of
> intuitive red-flag, which I think is the same point you are making?

I agree with you on this. This is among the terms that we neglect when
doing alchemical calculations in an isobaric simulations. If you decouple n
particles among N and have a barostat set at pressure P0, you will generate
an ensemble for the (N-n) particles at pressure P = P0 - Pn, where Pn is
the kinetic pressure from just n particles at the given volume and
temperature. If I get my orders of magnitude right: decoupling one particle
in a thousand from a condensed phase will underestimate the pressure by (on
the order of) 1 bar. That's something I can live with: I can say worse
things about my simulations.

> But on the other hand, if at the end-points you suddenly eliminate those
> degrees of freedom completely, doesn't that create a discontinuity in the
> transformation, which is a bad thing and source of much misery?

Unless you do TI, it's not a problem in and of itself: other estimators
explicitly give FE differences between discrete states. The tricky part may
be to account for that explicitly in the free energy estimator.

Probably an idiotic question from someone with limited physics
> understanding, but I suppose non-integer degrees of freedom are disallowed
> (assuming similar fractional counting of mass and velocity)?

Nothing prevents us from using a fractional number when calculating kinetic
pressure, although it doesn't have much physical meaning. That's pretty
much the spirit of alchemical transformations. Again, I'd be totally happy
with it if the estimators were rewritten with that in mind.


> On Thu, Nov 26, 2015 at 1:00 PM, Jérôme Hénin <>
> wrote:
>> Brian,
>> I might be missing something, but I'd say the degrees of freedom of
>> non-interacting particles should be counted for the purpose of kinetic
>> pressure calculation.
>> Jerome
>> On 25 November 2015 at 17:31, Brian Radak <> wrote:
>>> After some griping about this, I've finally implemented a (preliminary)
>>> correction to the Lennard-Jones tail correction that accounts for
>>> alchemical modifications. Once this is integrated with other improvements
>>> to the alchemical code, I hope this will become part of the 2.11 release.
>>> However, I recently noticed that a similar problem crops up in the
>>> degrees of freedom calculation. That is, alchemical atoms get counted at
>>> the endpoints even when they are only ideal gas particles. This was obvious
>>> when I started double checking single coordinate endpoint energies and
>>> pressures with dual coordinate alchemical energies and pressures; that is,
>>> the energies match but the pressures do not quite match.
>>> The error is admittedly much less than 0.1%, as multiplying a "more
>>> different" large number by a small number is still just another "kind of
>>> large" number. Nonetheless, one could view this as an error in the
>>> specified target pressure for an alchemical simulation (i.e. the pressure
>>> you input is not the pressure you simulate). Then again, this behavior
>>> might be exactly what one is expecting, depending on how one draws the
>>> thermodynamic cycle.
>>> I guess my question for the community is, does this matter? How do
>>> people expect degrees of freedom to be determined? Do people usually draw
>>> their cycles such that non-interacting particles should not contribute?
>>> This might not be the case, for example, in ligand binding calculations
>>> where the ligand continues to interact with its own images (although in
>>> that case, one essentially has two simulations going at the same time when
>>> the ligand is decoupled).
>>> Brian
>>> --
>>> Brian Radak
>>> Theta Early Science Program Postdoctoral Appointee
>>> Leadership Computing Facility
>>> Argonne National Laboratory
>>> 9700 South Cass Avenue
>>> Building 240, 1.D.16
>>> Lemont, IL 60439-4871
>>> Tel: 630/252-8643
>>> email:
> --
> Aron Broom M.Sc
> PhD Student
> Department of Chemistry
> University of Waterloo

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