[gmx-users] Hamiltonian replica exchange with solute tempering in 5.x version (bug?)

[呂宗諭]

Dear all,

I would appreciate you to give me any comments or share your experience on
the question below.

I am trying to run Hamiltonian replica exchange with solute tempering
(H-REST) in either 5.02 or 5.04 version to speed up the conformation
sampling of my protein along with a caging small molecule. I made some
changes in the force field parameters and used free energy function to
effectively realize H-REST.
However, after I prepared my equilibrated systems with different lambda
values and tried to run H-REST, mdrun keeps saying that properties of every
system are all the same.
I also found a weird thing, not sure if it's a bug. All of the mdout.mdp
files from different equilibrated systems have different lambda values at
the beginning. However, after they are combined to run H-REST, the .log
files turn out to have identical lambda values. The values are always that
of the last replica (higher effective temperature).

Here are an example of the mdp options I tried and the outcomes (.log file).
Any other variants will still just make every replica the same as the last
replica.

mdp option for replica 1

Free-energy = yes

Init-lambda-state = 0

fep-lambdas = 0

coul-lambdas = *0*

couple-moltype = Other2

nstdhdl = 0

couple-lambda0 = vdw-q

couple-lambda1 = vdw

couple-intramol = yes

mdp option for replica 8

Free-energy = yes
Init-lambda-state = 0
fep-lambdas = 0
coul-lambdas = *0.577*
couple-moltype = Other2
nstdhdl = 0
couple-lambda0 = vdw-q
couple-lambda1 = vdw
couple-intramol = yes


.log file of replica 1

        fep-lambdas =            0

       mass-lambdas =            0

       coul-lambdas =        *0.577*

        vdw-lambdas =            0

     bonded-lambdas =
  restraint-lambdas =            0

temperature-lambdas =            0


.log file of replica 8

        fep-lambdas =            0

       mass-lambdas =            0

       coul-lambdas =        *0.577*

        vdw-lambdas =            0

     bonded-lambdas =            0

  restraint-lambdas =            0

temperature-lambdas =            0

I've also tried the following mdp option according to Michael's advice.
https://mailman-1.sys.kth.se/pipermail/gromacs.org_gmx-users/2013-August/083430.html

Free-energy = yes
Init-lambda-state = 0
fep-lambdas = 0 0 0 0 0 0 0 0
coul-lambdas = 0 0.163 0.280 0.369 0.438 0.493 0.539 0.577
dhdl-derivatives = no
couple-moltype = Other2
nstdhdl = 0
couple-lambda0 = vdw-q
couple-lambda1 = vdw
couple-intramol = yes

but still not working.

If this is really a bug not just a mistake of my wrong settings, maybe I
should try PLUMED plug-in to invoke H-REST instead.

Thanks for your reading
Best regards,

Tony