GROMACS version: 2023

GROMACS modification: Yes/No

hello, I have applied a smd simulation between a cyclic peptide nanotube and a drug molecule. During 10 ns run, about 6th ns, the reference group that I pull the drug from it (ring one which name is cycle1 here) separates from the tube and the distance becomes more than its threshold and simulation is ceased. How can I stop this happening? I mean the separation? Can applying restraint on this ring help? Now It equals to 1000 for both backbone and sidechain restraints.

here is my pull.mdp file:

title = Umbrella pulling simulation

define = -DPOSRES

; Run parameters

integrator = md

dt = 0.002

tinit = 0

nsteps = 2500000 ; 500 ps

nstcomm = 10

; Output parameters

nstxout = 1000 ; every 10 ps

nstvout = 1000

nstfout = 500

nstxtcout = 500 ; every 1 ps

nstenergy = 500

; Bond parameters

constraint_algorithm = lincs

constraints = h-bonds

continuation = yes ; continuing from NPT

; Single-range cutoff scheme

cutoff-scheme = Verlet

nstlist = 5

ns_type = grid

rlist = 1.4

rcoulomb = 1.4

rvdw = 1.4

; PME electrostatics parameters

coulombtype = PME

fourierspacing = 0.12

fourier_nx = 0

fourier_ny = 0

fourier_nz = 0

pme_order = 4

ewald_rtol = 1e-5

optimize_fft = yes

; Berendsen temperature coupling is on in two groups

Tcoupl = v-rescale

tc_grps = Protein_drug lipid water_ions

tau_t = 1.0 1.0 1.0

ref_t = 300 300 300

; Pressure coupling is on

Pcoupl = c-rescale

pcoupltype = semiisotropic

tau_p = 1.0

compressibility = 4.5e-5 4.5e-5

ref_p = 1.0 1.0

refcoord_scaling = com

; Generate velocities is off

gen_vel = no

; Periodic boundary conditions are on in all directions

pbc = xyz

; Long-range dispersion correction

DispCorr = EnerPres

; Pull code

pull = yes

pull_ncoords = 1 ; only one reaction coordinate

pull_ngroups = 2 ; two groups defining one reaction coordinate

pull_group1_name = cycle1

pull_group2_name = drug

pull_coord1_type = umbrella ; harmonic potential

pull_coord1_geometry = direction ; simple distance increase

pull_coord1_vec = 0 0 -1

pull_coord1_groups = 1 2

pull_coord1_start = yes ; define initial COM distance > 0

pull_coord1_rate = 0.001 ; 0.01 nm per ps = 10 nm per ns

pull_coord1_k = 1000 ; kJ mol^-1 nm^-2