Re: [AMBER] Lambda Exchange

From: Jeff Wereszczynski <>
Date: Wed, 8 Oct 2014 13:50:31 -0500

Hi Jason,

OK, I'll disable the error checking and proceed with caution :)

And yes, the thermodynamic cycle works perfectly fine if you scale
intramolecular non-bonded interactions as well as intermolecular
interactions. The reason I ask is that in some systems it can help
convergence if you left the intramolecular interactions on, since this
represents a smaller perturbation to the system. Most of the time removing
the intramolecular interactions should be fine though, but I wanted to ask.

Thanks for your help!

Jeff Wereszczynski
Assistant Professor of Physics
Illinois Institute of Technology

On Wed, Oct 8, 2014 at 1:30 PM, Jason Swails <> wrote:

> On Wed, 2014-10-08 at 12:23 -0500, Jeff Wereszczynski wrote:
> > Hi Jason,
> >
> >
> >
> > Thanks for your response. To follow up:
> >
> >
> > 1. I can surely edit the prmtop files as you suggest. After I sent
> > this email it occurred to me that this will of course modify not only
> > the inter-molecular electrostatics, but also the intra-molecular
> > electrostatics. Is there a straightforward way to keep the
> > intra-molecular electrostatics on while scaling the energy terms
> > between the ligand and the rest of the system?
> No, but why is this necessary? I think the thermodynamics works out
> fine if the charges scale completely (I actually don't know if that's
> true for your proposed scheme). In fact, with PME this would be very
> difficult to accomplish anyway, since the reciprocal sum is not
> decomposable this way at all. (Effectively what you'd have to do is
> subtract out the reciprocal space contribution that's "wrong" and add
> back in the missing part of the direct-space -- akin to how the
> self-interaction energy and particle exclusions are done).
> >
> >
> > 2. You said "to use softcore TI," however I can't use the normal TI
> > commands with H-REMD (this is the root of most of my issues). When I
> > try to do this, I get the following error:
> >
> >
> > | ERROR: TI is incompatible with REMD
> Ah, then I see the confusion. :) I was not aware that error check was
> there. This is, I believe, a side effect of disjoint, over-cautious
> development efforts by graduate students. Joe Kaus wrote the TI
> implementation while I wrote the REMD implementation (~1 yr. earlier).
> So one of the following two things happened:
> 1) Joe was uncertain whether TI and REMD would work together in pmemd,
> since they didn't in sander. So he erred on the side of caution and
> prevented them from running together.
> 2) Joe knows something I don't. Namely, exactly why the two are
> incompatible in pmemd.
> So what I would suggest is disable this warning (comment that part of
> the code out in $AMBERHOME/src/pmemd/src/mdin_ctrl_dat.F90 and
> recompile). Just know that you are embarking into uncharted waters
> here. Waters I've wanted to investigate myself, but just haven't found
> the time.
> I don't see anything glaringly wrong with your input (you may need more
> than 2 lambda replicas -- you'll have to have a look at the exchange
> success rate to tell that).
> You can also use multi-dimensional REMD with H-REMD in one dimension
> (the lambda dimension) and T-REMD in the other... Just a thought.
> Good luck!
> Jason
> P.S. I would be interested to hear any successes or challenges you have
> with this approach.
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
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Received on Wed Oct 08 2014 - 12:00:03 PDT
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