GROMACS version: 2022.1

GROMACS modification: No

Dear users,

I need to use a simulated annealing protocol in order to understand the “important” interactions ligand/protein. Checking in the literature I found out that many researcher use a vdW scale factor during the cooling phase of the simulated annealing, in details they write: “Successively temperature was linearly reduced to 300 K in 5 ps, and, concurrently, the vdW scale factor have been similarly increased from its initial value (0.1) to its final value (1.0)”

From what i understood the point is to let the ligand “free” during the firsts moments of the cooling phase and than slowly slowly increase the restraints.

I’d like to know how to setup the .mdp file.

For now I arrived here, but I’m not sure that these parameters will give me the desidered result.

Here my .mdp file (I’m not sure about the vdW section).

; Run parameters

integrator = md ; leap-frog integrator

nsteps = 2500000 ; 2 * 2000000 = 5000 ps (5 ns)

dt = 0.002 ; 2 fs

; Output control

nstxout = 0 ; suppress bulky .trr file by specifying

nstvout = 0 ; 0 for output frequency of nstxout,

nstfout = 0 ; nstvout, and nstfout

nstenergy = 1000 ; save energies every 2.0 ps

nstlog = 1000 ; update log file every 2.0 ps

nstxout-compressed = 1000 ; save compressed coordinates every 2.0 ps

compressed-x-grps = System ; save the whole system

; Bond parameters

continuation = yes ; Restarting after NPT

constraint_algorithm = lincs ; holonomic constraints

constraints = h-bonds ; bonds involving H are constrained

lincs_iter = 1 ; accuracy of LINCS

lincs_order = 4 ; also related to accuracy

; Neighborsearching

cutoff-scheme = Verlet ; Buffered neighbor searching

ns_type = grid ; search neighboring grid cells

nstlist = 10 ; 20 fs, largely irrelevant with Verlet scheme

rcoulomb = 1.0 ; short-range electrostatic cutoff (in nm)

; Electrostatics

coulombtype = PME ; Particle Mesh Ewald for long-range electrostatics

pme_order = 4 ; cubic interpolation

fourierspacing = 0.16 ; grid spacing for FFT

; Van der Walls

vdwtype = cutoff

vdw-modifier = force-switch

rvdw-switch = 0.1

rvdw = 1

; Temperature coupling is on

tcoupl = V-rescale ; modified Berendsen thermostat

tc-grps = Protein_NON1 Water ; two coupling groups - more accurate

tau_t = 0.1 0.1 ; time constant, in ps

ref_t = 300 300 ; reference temperature, one for each group, in K

; Pressure coupling is on

pcoupl = Parrinello-Rahman ; Pressure coupling on in NPT

pcoupltype = isotropic ; uniform scaling of box vectors

tau_p = 2.0 ; time constant, in ps

ref_p = 1.0 ; reference pressure, in bar

compressibility = 4.5e-5 ; isothermal compressibility of water, bar^-1

; Periodic boundary conditions

pbc = xyz ; 3-D PBC

; Dispersion correction

DispCorr = EnerPres ; account for cut-off vdW scheme

; Velocity generation

gen_vel = no ; Velocity generation is off

; Simulated annealing

annealing = periodic periodic

annealing_npoints = 6 6

annealing_time = 0 10 18 22 42 50 0 10 18 22 42 50

annealing_temp = 300 300 500 500 300 300 300 300 500 500 300 300