Re: Bug advisory and workaround: alchemical FEP with IDWS can give wrong comparison energies

From: yjcoshc (
Date: Fri Nov 05 2021 - 11:53:09 CDT

Hi Jérôme,

In the development branch, I submitted a patch adding an option
"computeEnergies" to control the period of computing energy terms, which
defaults to be the "outputEnergies", so if someone uses

outputenergies          20
fullElectFrequency      4

and that will trigger an error to stop the simulation at start. You may
see for more details.

As for alchOutFreq, I personally agree to enforce it to be some multiple
of "outputenergies" for the GPU version, but I am not sure whether the
.fepout file will be deprecated since some people are in favor of the
log from stdout. In the case that alchOutFreq is not some multiples
ofcomputeEnergies, NAMD3 will show a warning like this:

Warning: The period of outputting energies relating to alchemical
transformations (alchOutFreq = 10) is not a multiple of the period of
computing energies (computeEnergies = 20). If alchOutFreq is smaller
than outputEnergies and computeEnergies is not defined, a better
solution is to set comp
uteEnergies explicitly and keep it the same as alchOutFreq. The
simulation will use the greatest common divisor of computeEnergies and
alchOutFreq as the period of energy evaluation.

I don't know whether the NAMD should just stop here or not, since the
greatest common divisor of "alchOutFreq" and "computeEnergies" is 10,
not a multiple of "fullElectFrequency". Hopefully you may propose a
better solution to this mess.


Haochuan Chen

On 11/5/21 11:12, Jérôme Hénin wrote:
> Hi all,
> Please be aware of a bug in current NAMD versions that can affect
> alchemical free energies computed using IDWS-style alchemical
> perturbations. Below I give workarounds to *get correct free energy
> values from existing data* affected by the issue, and to make any new
> simulation exempt from the issue.
> *Affected versions of NAMD:*
> 2.14, 3.x (non-CUDA version), and development versions until now.
> *Condition triggering the issue:*
> The issue occurs if multiple time-step is used and *alchOutFreq is
> greater than, but not a multiple of, fullElectFreq.*
> Unfortunately, the current default value of alchOutFreq (5) is likely
> to fulfill this condition.
> *Symptoms:*
> In this situation, some of the energy differences are computed
> erroneously - specifically, dE values computed at time steps that are
> not multiples of the outer time step include long-range dE values for
> the wrong target lambda.
> More generally, even without IDWS, alchOutFreq should probably
> /always/ be a multiple of fullElectFreq to ensure that comparison
> energies are as accurate as possible, and do not include stale
> long-range terms.
> *Fix and workaround:*
> For future simulations: define alchOutFreq as either 1 or a multiple
> of fullElectFreq.
> For existing simulations: re-analyze, discarding any data point from
> the fepout file where the time step number is not a multiple
> of fullElectFreq.
> *Diagnosis:*
> In doubt, the issue can be diagnosed for a specific dataset by
> histogramming forward and backward values of the electrostatic dE for
> an individual IDWS window. The bug will result in a characteristic
> bimodal distribution.
> I will submit a code patch very soon to fix this in a final way. In
> the meantime, please circulate the information to users who might be
> affected.
> Thanks to Ezry St. Iago-McRae (Brannigan lab, Rutgers Camden) for
> reporting the issue.
> Jérôme

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