Simulated annealing is controlled separately for each temperature group in GROMACS. The reference temperature is a piecewise linear function, but you can use an arbitrary number of points for each group, and choose either a single sequence or a periodic behaviour for each group. The actual annealing is performed by dynamically changing the reference temperature used in the thermostat algorithm selected, so remember that the system will usually not instantaneously reach the reference temperature!

annealing:

Type of annealing for each temperature group

no

No simulated annealing - just couple to reference temperature value.

single

A single sequence of annealing points. If your simulation is longer than the time of the last point, the temperature will be coupled to this constant value after the annealing sequence has reached the last time point.

periodic

The annealing will start over at the first reference point once the last reference time is reached. This is repeated until the simulation ends.

annealing-npoints:

A list with the number of annealing reference/control points used for each temperature group. Use 0 for groups that are not annealed. The number of entries should equal the number of temperature groups.

annealing-time:

List of times at the annealing reference/control points for each group. If you are using periodic annealing, the times will be used modulo the last value, i.e. if the values are 0, 5, 10, and 15, the coupling will restart at the 0ps value after 15ps, 30ps, 45ps, etc. The number of entries should equal the sum of the numbers given in annealing-npoints.

annealing-temp:

List of temperatures at the annealing reference/control points for each group. The number of entries should equal the sum of the numbers given in annealing-npoints.

let's use an example. Assume you have two temperature groups, set the group selections to annealing = single periodic, the number of points of each group to annealing-npoints = 3 4, the times to annealing-time = 0 3 6 0 2 4 6 and finally temperatures to annealing-temp = 298 280 270 298 320 320 298. The first group will be coupled to 298K at 0ps, but the reference temperature will drop linearly to reach 280K at 3ps, and then linearly between 280K and 270K from 3ps to 6ps. After this is stays constant, at 270K. The second group is coupled to 298K at 0ps, it increases linearly to 320K at 2ps, where it stays constant until 4ps. Between 4ps and 6ps it decreases to 298K, and then it starts over with the same pattern again, i.e. rising linearly from 298K to 320K between 6ps and 8ps.

#and

Use different names in your #ifdef blocks.

#ifdef STRONG_POSRES

#include "posre_25kcal.itp"

#endif

#ifdef WEAK_POSRES

#include "posre_5kcal.itp"

#endif

Set the "define" keyword in the .mdp file to the appropriate value to trigger the use of the different files.

Also, reading the GROMACS manual can help you more

https://manual.gromacs.org/documentation/

https://manual.gromacs.org/archive/4.6.5/online.html

Thanks a lot Rezvan Marjani for the detailed answer. I will try to use the #ifdef blocks which you have suggested and see if that works.

Good luck🌾 Dear @Sowmya Ramaswamy Krishnan

Dear Sowmya Ramaswamy Krishnan

I don't think you can use only one .mdp file.

One choice is having multiple .itp files with the different values of force constants as Rezvan Marjani suggested. In that case you will have to include all the #ifdef statements in your topology file, and use the define keyword in the .mdp file. If you have (taking from the comment above)

#ifdef STRONG_POSRES

#include "posre_25kcal.itp"

#endif

#ifdef WEAK_POSRES

#include "posre_5kcal.itp"

#endif

in your topology, then the .mdp file for the run with 25k constant will contain the line

define = -DSTRONG_POSRES

while the .mdp file for the run with 5k constant will contain the line

define = -DWEAK_POSRES

Although the two .mdp files may be identical in the other parameters, you still have to modify the define keyword.

A similar approach which doesn't require many .itp files and gives more freedom is to generate a .itp restraint file with one or more variables, something like

[ position_restraints ]

1 1 X_VALUE Y_VALUE Z_VALUE

2 1 X_VALUE Y_VALUE Z_VALUE

3 1 X_VALUE Y_VALUE Z_VALUE

4 1 X_VALUE Y_VALUE Z_VALUE

...

Then, you include this file (let's call it restraints_file.it) in the topology with the keyword to define it, e.g.

...

...

#include "topology_of_the_thing_you_want_to_restrain.itp"

#ifdef POSRES

#include "restraints_file.itp"

#endif

...

...

In this case, in your .mdp file you define the keyword to 'activate' the restraints and also define the values of the restraints, something like

define = -DPOSRES -DX_VALUE=alpha -DY_VALUE=beta -DZ_value=gamma

where here alpha, beta and gamma are the values for the force constants you want to use. In this case you are saying to GROMACS that you want to use the restraints (with -DPOSRES as you defined it in the topology) and then define the values to be used (note the -D in front of the parameter names).

In this way you need just one .itp file with the restraints defined and play with their values from the .mdp file. Again, each simulation will require a different .mdp file, that is an .mdp file where you modified the alpha/beta/gamma values to match the values you need.

If your question was related to achieve something like the annealing, that is, run a single equilibrium run while modifying during the run the value k of the restraints (if T = a, then k = A, if T = b, then k = B etc, so that during the anneal the values change alone) then I don't think it can be possible with GROMACS, but maybe I'm mistaken.

Hope this helps,

Nicola

Thank you Dr. Nicola Piasentin for the alternative approach. I tried the #ifdef blocks yesterday with the .mdp file, but it did not produce the desired result. I also think that what I'm trying to do is not possible in a single equilibrium run in GROMACS. So I'm instead trying to perform the equilibration in multiple steps instead of trying to automate the process using a single .mdp file. But your suggestion to use the following statement to define the force constants in a single line:

define = -DPOSRES -DX_VALUE=alpha -DY_VALUE=beta -DZ_value=gamma

is really helpful. I think this will avoid creation of multiple posre.itp files with the appropriate force constant values. Thanks a lot for the suggestion!