Re: [gmx-users] Free Energy Calculations: Error during minimization step.

[Abhishek Acharya]

Hello Wes,

I ran some more test simulations. I think the error is because I added
counterions to neutralize my system (it has a +2 charge) prior to the free
energy. Without the counterions, the simulations are running fine. Though,
I don't know whether such a behavior is expected. Such a setup (with
counterions) is not something unheard of.

Nevertheless, I read elsewhere that for solvation free energy calculation
of charged system, the uniform background charge as implemented in PME for
non-neutral systems may be desirable. Hence, I plan to run the simulations
without counterions.

Sincerely,
Abhishek




Abhishek Acharya
Research Associate,
Department of Molecular Nutrition
CSIR-Central Food Technological Research Institute,
Mysuru-570020

On Tue, Sep 12, 2017 at 5:22 PM, Wes Barnett  wrote:

> On Tue, Sep 12, 2017 at 12:17 AM, Abhishek Acharya <
> abhi117acha...@gmail.com
> > wrote:
>
> > Just to add to the above post, running a none to vdw-q tranformation
> using
> > the following parameters also results in the same error for simulation at
> > first lambda.
> >
>
>
> Do you get this error on a normal simulation as well? That is, if you run
> state 0 (with vdw and electrostatics on) without doing an free energy
> calculations, do you still get the error? Perhaps you are using too big a
> of a time step or your system is not equilibrated enough before using this
> time step. Or you may just have a bad starting configuration.
>
>
> >
> > 
> > 
> > 
> > vdw_lambdas  = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40
> > 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.00 1.00
> 1.00
> > 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
> 1.00
> > 1.00 1.00
> > coul_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05 0.10
> 0.15
> > 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85
> 0.90
> > 0.95 1.00
> > ; We are not transforming any bonded or restrained interactions
> > bonded_lambdas   = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00
> > 0.00 0.00
> > restraint_lambdas= 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00
> > 0.00 0.00
> > ; Masses are not changing (particle identities are the same at lambda = 0
> > and lambda = 1)
> > mass_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00
> > 0.00 0.00
> > ; Not doing simulated temperting here
> > temperature_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00
> > 0.00 0.00
> > ; Options for the decoupling
> > sc-alpha = 0.5
> > sc-coul  = no   ; linear interpolation of Coulomb
> (none
> > in this case)
> > sc-power = 1
> > sc-sigma = 0.3
> > couple-moltype   = Protein  ; name of moleculetype to decouple
> > couple-lambda0   = none
> > couple-lambda1   = vdw-q
> > couple-intramol  = no
> > nstdhdl  = 10
> > 
> > 
> > 
> >
> > Thanks in advance.
> >
> > Abhishek Acharya
> > Research Associate,
> > Department of Molecular Nutrition
> > CSIR-Central Food Technological Research Institute,
> > Mysuru-570020
> >
> > On Tue, Sep 12, 2017 at 9:42 AM, Abhishek Acharya <
> > abhi117acha...@gmail.com>
> > wrote:
> >
> > > Hello GROMACS users,
> > >
> > > As Wes had advised previously in this thread, the issue with the vdw
> > > tranformations was rectified by removing the charges from the topology
> > > file. Thereafter, I also tried running free energy calculations using
> the
> > > following free-energy parameters:
> > >
> > > 
> > > 
> > > 
> > > free_energy  = yes
> > > init_lambda_state= 0
> > > delta_lambda = 0
> > > calc_lambda_neighbors= 1; only 

Re: [gmx-users] Free Energy Calculations: Error during minimization step.

[Wes Barnett]

On Tue, Sep 12, 2017 at 12:17 AM, Abhishek Acharya  wrote:

> Just to add to the above post, running a none to vdw-q tranformation using
> the following parameters also results in the same error for simulation at
> first lambda.
>


Do you get this error on a normal simulation as well? That is, if you run
state 0 (with vdw and electrostatics on) without doing an free energy
calculations, do you still get the error? Perhaps you are using too big a
of a time step or your system is not equilibrated enough before using this
time step. Or you may just have a bad starting configuration.


>
> 
> 
> 
> vdw_lambdas  = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40
> 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.00 1.00 1.00
> 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
> 1.00 1.00
> coul_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05 0.10 0.15
> 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90
> 0.95 1.00
> ; We are not transforming any bonded or restrained interactions
> bonded_lambdas   = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00
> restraint_lambdas= 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00
> ; Masses are not changing (particle identities are the same at lambda = 0
> and lambda = 1)
> mass_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00
> ; Not doing simulated temperting here
> temperature_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00
> ; Options for the decoupling
> sc-alpha = 0.5
> sc-coul  = no   ; linear interpolation of Coulomb (none
> in this case)
> sc-power = 1
> sc-sigma = 0.3
> couple-moltype   = Protein  ; name of moleculetype to decouple
> couple-lambda0   = none
> couple-lambda1   = vdw-q
> couple-intramol  = no
> nstdhdl  = 10
> 
> 
> 
>
> Thanks in advance.
>
> Abhishek Acharya
> Research Associate,
> Department of Molecular Nutrition
> CSIR-Central Food Technological Research Institute,
> Mysuru-570020
>
> On Tue, Sep 12, 2017 at 9:42 AM, Abhishek Acharya <
> abhi117acha...@gmail.com>
> wrote:
>
> > Hello GROMACS users,
> >
> > As Wes had advised previously in this thread, the issue with the vdw
> > tranformations was rectified by removing the charges from the topology
> > file. Thereafter, I also tried running free energy calculations using the
> > following free-energy parameters:
> >
> > 
> > 
> > 
> > free_energy  = yes
> > init_lambda_state= 0
> > delta_lambda = 0
> > calc_lambda_neighbors= 1; only immediate neighboring windows
> > ; Vectors of lambda specified here
> > ; Each combination is an index that is retrieved from for each simulation
> > coul_lambdas  = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40
> > 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.00 1.00
> 1.00
> > 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
> 1.00
> > 1.00 1.00
> > vdw_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05 0.10
> 0.15
> > 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85
> 0.90
> > 0.95 1.00
> > bonded_lambdas   = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00
> > 0.00 0.00
> > restraint_lambdas= 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> > 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 

Re: [gmx-users] Free Energy Calculations: Error during minimization step.

[Abhishek Acharya]

Just to add to the above post, running a none to vdw-q tranformation using
the following parameters also results in the same error for simulation at
first lambda.




vdw_lambdas  = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40
0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.00 1.00 1.00
1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
1.00 1.00
coul_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05 0.10 0.15
0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90
0.95 1.00
; We are not transforming any bonded or restrained interactions
bonded_lambdas   = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00
restraint_lambdas= 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00
; Masses are not changing (particle identities are the same at lambda = 0
and lambda = 1)
mass_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00
; Not doing simulated temperting here
temperature_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00
; Options for the decoupling
sc-alpha = 0.5
sc-coul  = no   ; linear interpolation of Coulomb (none
in this case)
sc-power = 1
sc-sigma = 0.3
couple-moltype   = Protein  ; name of moleculetype to decouple
couple-lambda0   = none
couple-lambda1   = vdw-q
couple-intramol  = no
nstdhdl  = 10




Thanks in advance.

Abhishek Acharya
Research Associate,
Department of Molecular Nutrition
CSIR-Central Food Technological Research Institute,
Mysuru-570020

On Tue, Sep 12, 2017 at 9:42 AM, Abhishek Acharya 
wrote:

> Hello GROMACS users,
>
> As Wes had advised previously in this thread, the issue with the vdw
> tranformations was rectified by removing the charges from the topology
> file. Thereafter, I also tried running free energy calculations using the
> following free-energy parameters:
>
> 
> 
> 
> free_energy  = yes
> init_lambda_state= 0
> delta_lambda = 0
> calc_lambda_neighbors= 1; only immediate neighboring windows
> ; Vectors of lambda specified here
> ; Each combination is an index that is retrieved from for each simulation
> coul_lambdas  = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40
> 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.00 1.00 1.00
> 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
> 1.00 1.00
> vdw_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05 0.10 0.15
> 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90
> 0.95 1.00
> bonded_lambdas   = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00
> restraint_lambdas= 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00
> mass_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00
> temperature_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00
> ; Options for the decoupling
> sc-alpha  

Re: [gmx-users] Free Energy Calculations: Error during minimization step.

[Abhishek Acharya]

Hello GROMACS users,

As Wes had advised previously in this thread, the issue with the vdw
tranformations was rectified by removing the charges from the topology
file. Thereafter, I also tried running free energy calculations using the
following free-energy parameters:


free_energy  = yes
init_lambda_state= 0
delta_lambda = 0
calc_lambda_neighbors= 1; only immediate neighboring windows
; Vectors of lambda specified here
; Each combination is an index that is retrieved from for each simulation
coul_lambdas  = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40
0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.00 1.00 1.00
1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
1.00 1.00
vdw_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05 0.10 0.15
0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90
0.95 1.00
bonded_lambdas   = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00
restraint_lambdas= 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00
mass_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00
temperature_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00
; Options for the decoupling
sc-alpha = 0.5
sc-coul  = no   ; linear interpolation of Coulomb (none
in this case)
sc-power = 1
sc-sigma = 0.3
couple-moltype   = Protein  ; name of moleculetype to decouple
couple-lambda0   = vdw-q
couple-lambda1   = none
couple-intramol  = no
nstdhdl  = 10



As you can see, I want to first annihilate the charges, followed by a vdw
tranformation, using a total of 41 lambdas. Since both charges and vdw are
being interpolated, the topology files contain the normal charges for the
transformed molecule. This setup is similar to what Wes had suggested in a
previous response to this thread.

The issue is that I am facing the exactly the same error in minimization
step at final lambda state where both vdw and electrostatics are turned off.

--
Program gmx mdrun, VERSION 5.1.2
Source code file:
/home/bp-lab/Downloads/gromacs-5.1.2/src/gromacs/mdlib/constr.cpp, line: 555

Fatal error:

step 10: Water molecule starting at atom 120 can not be settled.
Check for bad contacts and/or reduce the timestep if appropriate.

For more information and tips for troubleshooting, please check the GROMACS
website at http://www.gromacs.org/Documentation/Errors

---

Now, what I understood is that in case of just the vdw transformation,
since we are not calculating any electrostatics, the charges should be zero
in topology file. Whereas, in case of just the charge transformation, the
charges are required in the topology file as charges are interpolated in
this step. And performing the simulation as such give no errors.

I do not understand why the error is surfacing in case of a [vdw-q] to
[none ] tranformation., especially now that the charges are gradually
decoupled prior to decoupling the vdw interactions.  Any help will be
greatly appreciated.

Sincerely,
Abhishek


Abhishek Acharya
Research Associate,
Department of Molecular Nutrition
CSIR-Central Food Technological Research Institute,
Mysuru-570020

On Sun, Sep 10, 2017 at 8:02 AM, Abhishek Acharya 
wrote:

>
>
>
> You can do them separately, but the charges need to have been turned off
> for the molecule you are transforming for the second step when turning off
> vdw. In other words, all charges must be 0.0 for the 

Re: [gmx-users] Free Energy Calculations: Error during minimization step.

[Abhishek Acharya]

You can do them separately, but the charges need to have been turned off
for the molecule you are transforming for the second step when turning off
vdw. In other words, all charges must be 0.0 for the molecule in the
topology file for the vdw transformation. Is that what you've done?

Justin's tutorial gives an explanation on why this needs to be done, and in
his topology he had all charges at 0.0 in the methane topology file.


Okey, one thing that I presumed while performing the second transformation
is that it is sufficient to 'turn-off' charge electrostatics just by
stating c-lambda0=none and c-lambda1 = vdw (or vice-versa). It doesn't
matter if the topology files have the charges or not. Therefore, i had
included the charges in my topology file.

Then this explains the problem in my case. Thank you so much Wes for
clarifying that out.

Sincerely,
Abhishek Acharya
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Re: [gmx-users] Free Energy Calculations: Error during minimization step.

[Wes Barnett]

On Sat, Sep 9, 2017 at 10:10 AM, Abhishek Acharya 
wrote:

> Hello Wes,
>
> Thanks for your reply.
>
> Sorry, I did not understand why we need to turn off charges first and then
> vdw, if the are performing both steps separately.
>
> I was attempting to perform the vdw and charge transformations separately.
> So for the vdw transformation, if I use c-lambda0=vdw
> and c-lambda1=none, I think that would signal gromacs that the
> electrostatics are turned off at all lambda values.and the vdw interpolate
> from full strength at lambda=0 to none at lambda=1.0
>


You can do them separately, but the charges need to have been turned off
for the molecule you are transforming for the second step when turning off
vdw. In other words, all charges must be 0.0 for the molecule in the
topology file for the vdw transformation. Is that what you've done?

Justin's tutorial gives an explanation on why this needs to be done, and in
his topology he had all charges at 0.0 in the methane topology file.


-- 
James "Wes" Barnett
Postdoctoral Research Scientist
Department of Chemical Engineering
Kumar Research Group 
Columbia University
w.barn...@columbia.edu
http://wbarnett.us
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Re: [gmx-users] Free Energy Calculations: Error during minimization step.

[Abhishek Acharya]

Hello Wes,

Thanks for your reply.

Sorry, I did not understand why we need to turn off charges first and then
vdw, if the are performing both steps separately.

I was attempting to perform the vdw and charge transformations separately.
So for the vdw transformation, if I use c-lambda0=vdw
and c-lambda1=none, I think that would signal gromacs that the
electrostatics are turned off at all lambda values.and the vdw interpolate
from full strength at lambda=0 to none at lambda=1.0

This is similar to what is done in Justin's free energy tutorial, that you
have provide the link to.


Has the charge been turned off for this series of simulations? You should
generally turn electrostatics off through a series of free energy
simulations and then turn off VDW while the charge is off.


For the charge annihilation transformation. I used couple-lambda0=vdw-q and
couple-lambda1= vdw.
I presume that  in this case the vdw interactions are never turned off,
while the charges interpolate from full strength at lambda=0 to none at
lambda=1.0.

Kindly correct me if there some mistake in my understanding.


>
> Looking for the some advice on how to proceed from here.
>

I do something like this:

vdw-lambdas  = 0.00 0.00 0.00 0.00 0.00 0.10 0.20 0.30 0.40
0.50 0.60 0.70 0.80 0.90 1.00
coul-lambdas = 0.00 0.25 0.50 0.75 1.00 1.00 1.00 1.00 1.00
1.00 1.00 1.00 1.00 1.00 1.00
couple-lambda0   = vdw-q
couple-lambda1   = none


Yes I have seen this..I thought the only utility this has is that both vdw
and charge transformations can be done in one shot.
I was planning to run this way, but after the aforesaid (separate)
calculations run correctly.

But, I still don't understand the reason for the above issue in vdw
transformation step. Any clarification will be very helpful.

Sincerely,
Abhishek Acharya
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Re: [gmx-users] Free Energy Calculations: Error during minimization step.

[Wes Barnett]

On Sat, Sep 9, 2017 at 2:09 AM, Abhishek Acharya 
wrote:

> Dear GROMACS users,
>
> I am trying to estimate the free energy of solvation for a ion. But, I am
> facing a problem while running simulations for the deltaG_LJ calculation.
> The simulation at vdw_lambda=1.0 crashes during the steepest-descent
> minimization step, with the following error.
>
> ---
> Program gmx mdrun, VERSION 5.1.2
> Source code file:
> /home/bp-lab/Downloads/gromacs-5.1.2/src/gromacs/mdlib/constr.cpp, line:
> 555
>
> Fatal error:
>
> step 10: Water molecule starting at atom 120 can not be settled.
> Check for bad contacts and/or reduce the timestep if appropriate.
>
> For more information and tips for troubleshooting, please check the GROMACS
> website at http://www.gromacs.org/Documentation/Errors
> ---
>
> The free energy parameters I used for this run are as follows:
> 
> *
> free_energy  = yes
> couple-moltype   = Protein
> couple-lambda0   = vdw
> couple-lambda1   = none
> couple-intramol  = no
> init-lambda  = -1
> init_lambda_state= 20
> delta_lambda = 0
> nstdhdl  = 10
> fep-lambdas  =
> mass_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> coul_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> vdw_lambdas  = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40
> 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00
> bonded_lambdas   = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> restraint_lambdas= 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> temperature_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> calc_lambda_neighbors= 1
> init-lambda-weights  =
> dhdl-print-energy= no
> sc-alpha = 0.5
> sc-power = 1
> sc-r-power   = 6
> sc-sigma = 0.3
> sc-coul  = no
> separate-dhdl-file   = yes
> dhdl-derivatives = yes
> dh_hist_size = 0
> dh_hist_spacing  = 0.1
> 
> *
>
> Out of curiosity, I also ran simulations for a reverse transformation with
> the following parameters (and I hope they are correct):
>
> 
> *
> free_energy  = yes
> couple-moltype   = Protein
> couple-lambda0   = none
> couple-lambda1   = vdw
> couple-intramol  = no
> init-lambda  = -1
> init_lambda_state= 0
> delta_lambda = 0
> nstdhdl  = 10
> fep-lambdas  =
> mass_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> coul_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> vdw_lambdas  = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40
> 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00
> bonded_lambdas   = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> restraint_lambdas= 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> temperature_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> calc_lambda_neighbors= 1
> init-lambda-weights  =
> dhdl-print-energy= no
> sc-alpha = 0.5
> sc-power = 1
> sc-r-power   = 6
> sc-sigma = 0.3
> sc-coul  = no
> separate-dhdl-file   = yes
> dhdl-derivatives = yes
> dh_hist_size = 0
> dh_hist_spacing  = 0.1
> 
> *
> Intriguingly, I this case I got the exact error as above, but this time at
> lambda=0.
>

That make sense, since in both cases the vdw interactions are off in both
situations (couple-lambda0 or couple-lambda1 = none).



> ---
> Program gmx mdrun, VERSION 5.1.2

[gmx-users] Free Energy Calculations: Error during minimization step.

[Abhishek Acharya]

Dear GROMACS users,

I am trying to estimate the free energy of solvation for a ion. But, I am
facing a problem while running simulations for the deltaG_LJ calculation.
The simulation at vdw_lambda=1.0 crashes during the steepest-descent
minimization step, with the following error.

---
Program gmx mdrun, VERSION 5.1.2
Source code file:
/home/bp-lab/Downloads/gromacs-5.1.2/src/gromacs/mdlib/constr.cpp, line: 555

Fatal error:

step 10: Water molecule starting at atom 120 can not be settled.
Check for bad contacts and/or reduce the timestep if appropriate.

For more information and tips for troubleshooting, please check the GROMACS
website at http://www.gromacs.org/Documentation/Errors
---

The free energy parameters I used for this run are as follows:
*
free_energy  = yes
couple-moltype   = Protein
couple-lambda0   = vdw
couple-lambda1   = none
couple-intramol  = no
init-lambda  = -1
init_lambda_state= 20
delta_lambda = 0
nstdhdl  = 10
fep-lambdas  =
mass_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
coul_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
vdw_lambdas  = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40
0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00
bonded_lambdas   = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
restraint_lambdas= 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
temperature_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
calc_lambda_neighbors= 1
init-lambda-weights  =
dhdl-print-energy= no
sc-alpha = 0.5
sc-power = 1
sc-r-power   = 6
sc-sigma = 0.3
sc-coul  = no
separate-dhdl-file   = yes
dhdl-derivatives = yes
dh_hist_size = 0
dh_hist_spacing  = 0.1
*

Out of curiosity, I also ran simulations for a reverse transformation with
the following parameters (and I hope they are correct):

*
free_energy  = yes
couple-moltype   = Protein
couple-lambda0   = none
couple-lambda1   = vdw
couple-intramol  = no
init-lambda  = -1
init_lambda_state= 0
delta_lambda = 0
nstdhdl  = 10
fep-lambdas  =
mass_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
coul_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
vdw_lambdas  = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40
0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00
bonded_lambdas   = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
restraint_lambdas= 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
temperature_lambdas  = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
calc_lambda_neighbors= 1
init-lambda-weights  =
dhdl-print-energy= no
sc-alpha = 0.5
sc-power = 1
sc-r-power   = 6
sc-sigma = 0.3
sc-coul  = no
separate-dhdl-file   = yes
dhdl-derivatives = yes
dh_hist_size = 0
dh_hist_spacing  = 0.1
*
Intriguingly, I this case I got the exact error as above, but this time at
lambda=0.
---
Program gmx mdrun, VERSION 5.1.2
Source code file:
/home/bp-lab/Downloads/gromacs-5.1.2/src/gromacs/mdlib/constr.cpp, line: 555

Fatal error:

step 10: Water molecule starting at atom 120 can not be settled.
Check for bad contacts and/or reduce the timestep if appropriate.

For more information and tips for troubleshooting, please check the GROMACS
website at http://www.gromacs.org/Documentation/Errors
---