[gmx-users] Re: 1-4 interactions free energy calculations

Michael Shirts mrshirts at gmail.com
Wed Jun 26 03:04:20 CEST 2013

Hi, Sonia-

Gromacs 4.6.2 (some bug fixes vs 4.6.1) with the example files you
point out from Alchemistry.org should work well for expanded ensemble.
 David Mobley and I have been validating expanded ensemble and replica
exchange, and the files posted there now are stable for all sizes of
systems, and give reasonable results.  expanded ensemble with NPT is
somewhat unstable for smaller systems (1000 total molecules), though
is much more stable for larger systems -- the posted parameter should

However, note that you have to be careful with expanded ensemble, as
the weights can sometime converge to a poor value.

I'm working on some more guidance on expanded ensemble besides the
examples on Alchemistry.org, but it may take a few weeks.  Check back
in a few weeks for some more information on Alchemistry.org.

On Tue, Jun 25, 2013 at 4:36 PM, Sonia Aguilera
<sm.aguilera37 at uniandes.edu.co> wrote:
> Hi Justin,
> Thank you for your answer. I’m performing several tests to see what is the
> best for my system. The reason I decided not to couple the intramolecular
> interactions is because I think that the annihilation of the molecule will
> lead to very extreme configurations and that will affect my phase-space
> overlap. I know I can just increase the number of intermediate states, but I
> wanted to first test my theory. Also, I have limited resources to run.
> There is a gap between the indirect and direct calculation methods  for my
> system. If I set up couple-intramol=no, then I can´t use domain
> decomposition but particle decomposition in all simulations (charge groups
> are too big, and there is no domain decomposition… ) and I got the 1-4
> interactions warning. If I restrain the h-bonds, then the minimization
> converges but not to Fmax less than 100 in only 499 steps and 12 minutes (8
> cores machines). If I continue and run the NVT stabilization, then it takes
> 17h20min to complete only 100 ps, and I still got the 1-4 interactions
> warning. I still have to run the NPT and 3 ns MD, which will take too much
> time. I think it worth it  because I think it will help with the phase-space
> overlap, and I will only have to perform 20 series of simulations (vdw and
> coulomb separately) to get the free energy change.
> On the other hand, if I set up couple-intramol=yes, then I have to run 20
> extra simulations in vacuo to counter the annihilation effect. I think that
> it will also affect the phase-space overlap. The good thing is that I can
> use domain decomposition and the minimization converges to machine precision
> (takes 7000 steps and around 40 minutes in a machine with the same
> characteristics that the previous one). Also, the same 100-ps NVT takes only
> 3h20min. If I think of the overall picture, it seems that the total time I
> will spend doing dd (coupleintramol=yes) rather than pd (coupleintramol=no)
> will be less. However I’m worried about the phase-space overlap and the
> available resources I have for running since it makes difficult to just
> increase the intermediate states.
> Also, I think I can try doing the same but with the 4.6.1 version. It looks
> like I can now couple both vdw and coulomb in the same simulation
> (http://www.alchemistry.org/wiki/GROMACS_4.6_example:_Direct_ethanol_solvation_free_energy).
> I have also wanted to try expanded ensemble to improve my sampling, but I
> have not found that much documentation about the implementation on gromacs.
> It would be great if you can provide an example.
> So, do you know another way to improve my sampling and the phase-space
> overlap that can help me to solve my problem?  Also, I’m working with a
> charged molecule. Would it help in any aspect if I neutralize the system?
> Thank you very much in advance,
> Best regards,
> Sonia Aguilera
> Graduate Assistant
> Department of Chemical Engineering
> Universidad de los Andes
> --
> View this message in context: http://gromacs.5086.x6.nabble.com/1-4-interactions-free-energy-calculations-tp5009364p5009378.html
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