GROMACS version: 2023.2-plumed_2.10.0_dev
GROMACS modification: No
Hello everyone,
I am applying AWH to study the permeation of a charged ligand (with -2 charge) through a DOPC bilayer. My setup is largely based on the following discussion:
https://gromacs.bioexcel.eu/t/using-awh-for-bilayer-permeability/6727
Following that thread, I tested several combinations of AWH parameters (e.g., awh1-dim1-diffusion, awh1-error-init, pull_coord1_k, and related settings). I have attached a short summary of the results from several 600 ns simulations. My main difficulty is that the ligand often becomes trapped on one side of the membrane or within the bilayer, with very few complete back-and-forth transitions. Consequently, the PMF is still changing noticeably after 600 ns, and I am unsure whether this is expected for a charged ligand or indicates that my AWH setup still needs improvement.
Before investing in much longer or multi-walker simulations, I would appreciate some guidance on whether my current approach is reasonable and which parameters you would recommend adjusting first. In particular, comments from AWH developers or experienced users would be greatly appreciated.
Thank you very much for your time. The attached files
summarizes the parameter sets and corresponding results.
Bests
Zahra
Here is mdp settings:
define = -DPOSRES_DOPC_P -DPOSRES_FC_LIPID=1000
integrator = md
dt = 0.002
nsteps = 300000000
nstxout = 5000
nstvout = 50000
nstfout = 50000
nstcalcenergy = 100
nstenergy = 1000
nstlog = 1000
nstxout-compressed = 5000
cutoff-scheme = Verlet
nstlist = 20
rlist = 1.4
vdwtype = Cut-off
rvdw = 1.4
coulombtype = PME
rcoulomb = 1.4
tcoupl = Nose-Hoover
tc_grps = SOLU MEMB SOLV
tau_t = 0.5 0.5 0.5
ref_t = 323 323 323
pcoupl = C-rescale
pcoupltype = semiisotropic
tau_p = 5.0
compressibility = 4.5e-5 4.5e-5
ref_p = 1.0 1.0
constraints = h-bonds
constraint_algorithm = LINCS
continuation = yes
gen_vel = no
nstcomm = 100
comm_mode = linear
comm_grps = SOLU_MEMB SOLV
pull = yes
pull_ncoords = 1
pull_ngroups = 2
pull_group1_name = MEMB
pull_group1_pbcatom = 9610
pull_group2_name = SOLU
pull_group2_pbcatom = 29
pull_nstxout = 100
pull_nstfout = 100
pull_coord1_groups = 1 2
pull_pbc_ref_prev_step_com = yes
pull_coord1_type = external-potential
pull_coord1_potential_provider = awh
pull_coord1_geometry = direction
pull_coord1_vec = 0 0 1
pull_coord1_dim = N N Y
pull_coord1_rate = 0
pull_coord1_start = yes
pull_coord1_k = 1000
awh = yes
awh_nstout = 50000
awh_potential = convolved
awh_nbias = 1
awh_nstsample = 100
awh_nsamples_update = 10
awh1_growth = exp-linear
awh1_target = constant
awh1_user_data = no
awh1_ndim = 1
awh1_dim1_coord_provider = pull
awh1_dim1_coord_index = 1
awh1_dim1_start = -4.0
awh1_dim1_end = 4.0
awh1_equilibrate_histogram = yes
awh1_dim1_force_constant = 75000
awh1_dim1_diffusion = 2e-3
awh1_error_init = 20