[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 <abhi117acharya at gmail.com>
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 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
>
>
>