GROMACS version: 2019.2
GROMACS modification: No
Hi everybody,
For the past couple of months I’ve been trying to use Gromacs to calculate the Absolute Binding Free Energy (ABFE) of a ligand to a protein-RNA complex via non-equilibrium thermodynamic integration (non-eq ti). I’ve regularly gotten a segmentation fault (core dumped) error when trying to run a short (15ns) production simulation of my ligand fully decoupled (VdW and coulombic interactions OFF) from the protein-RNA complex. I thought it was due to a really floppy RNA chain, so I implemented a new equilibration procedure–after energy minimization, before production simulation–involving position restraints first on all atoms in nvt, then all atoms in npt, and then all heavy atoms in npt. Doing this led to one successful mdrun production simulation, but two of them failed. One failed after 2.85ns, and the other failed at 7.95ns which leads me to believe that it’s probably not a question of a poorly equilibrated starting structure (although I could be wrong). What’s more frustrating to me is that there are no errors or warnings in the md.log files for both cases, and the only error message is in the job output file where it says:
“step 1429500, will finish Sun Sep 18 00:13:53 2022/var/spool/slurmd/job1002489/slurm_script: line 19: 383301 Segmentation fault (core dumped) gmx mdrun -v -s topol.tpr -ntomp 48 -pin on”
It’s the same case for the other one that failed but at a later time. I know that some Gromacs versions are finnicky about free energy mdrun things, and I stopped using the version of 2021 our lab has because of a similar issue (that was initially solved by me switching back to 2019). Any advice on this would be super helpful! I feel like I’ve been staring at this same problem for so long and I’m unsure about what else to do to for troubleshooting.
My mdp file:
;
; File ‘mdout.mdp’ was generated
; By user: ()
; On host:
; At date: Thu Sep 15 12:45:25 2022
;
; Created by:
; :-) GROMACS - gmx grompp, 2019.2 (-:
;
; Executable: /home//lab/gromacs/2019/2019.2-impi2018-fftw377-gcc550-cuda90/bin/gmx
; Data prefix: /home//lab/gromacs/2019/2019.2-impi2018-fftw377-gcc550-cuda90
; Working dir: ///ABFE/A3_OBM/state_B/03
; Command line:
; gmx grompp -f ABFE_prod.mdp -c npt2.gro -r npt2.gro -o topol.tpr -p topol.top
; VARIOUS PREPROCESSING OPTIONS
; Preprocessor information: use cpp syntax.
; e.g.: -I/home/joe/doe -I/home/mary/roe
include =
; e.g.: -DPOSRES -DFLEXIBLE (note these variable names are case sensitive)
define =
; RUN CONTROL PARAMETERS
integrator = sd
; Start time and timestep in ps
tinit = 0
dt = 0.002
nsteps = 7500000
; For exact run continuation or redoing part of a run
init-step = 0
; Part index is updated automatically on checkpointing (keeps files separate)
simulation-part = 1
; mode for center of mass motion removal
comm-mode = Linear
; number of steps for center of mass motion removal
nstcomm = 100
; group(s) for center of mass motion removal
comm-grps =
; LANGEVIN DYNAMICS OPTIONS
; Friction coefficient (amu/ps) and random seed
bd-fric = 0
ld-seed = -1
; ENERGY MINIMIZATION OPTIONS
; Force tolerance and initial step-size
emtol = 10
emstep = 0.01
; Max number of iterations in relax-shells
niter = 20
; Step size (ps^2) for minimization of flexible constraints
fcstep = 0
; Frequency of steepest descents steps when doing CG
nstcgsteep = 1000
nbfgscorr = 10
; TEST PARTICLE INSERTION OPTIONS
rtpi = 0.05
; OUTPUT CONTROL OPTIONS
; Output frequency for coords (x), velocities (v) and forces (f)
nstxout = 25000
nstvout = 25000
nstfout = 0
; Output frequency for energies to log file and energy file
nstlog = 25000
nstcalcenergy = 25000
nstenergy = 25000
; Output frequency and precision for .xtc file
nstxout-compressed = 25000
compressed-x-precision = 25000
; This selects the subset of atoms for the compressed
; trajectory file. You can select multiple groups. By
; default, all atoms will be written.
compressed-x-grps =
; Selection of energy groups
energygrps =
; NEIGHBORSEARCHING PARAMETERS
; cut-off scheme (Verlet: particle based cut-offs, group: using charge groups)
cutoff-scheme = Verlet
; nblist update frequency
nstlist = 10
; ns algorithm (simple or grid)
ns-type = grid
; Periodic boundary conditions: xyz, no, xy
pbc = xyz
periodic-molecules = no
; Allowed energy error due to the Verlet buffer in kJ/mol/ps per atom,
; a value of -1 means: use rlist
verlet-buffer-tolerance = 0.005
; nblist cut-off
rlist = 1.0
; long-range cut-off for switched potentials
; OPTIONS FOR ELECTROSTATICS AND VDW
; Method for doing electrostatics
coulombtype = PME
coulomb-modifier = Potential-shift-Verlet
rcoulomb-switch = 0
rcoulomb = 1.0
; Relative dielectric constant for the medium and the reaction field
epsilon-r = 1
epsilon-rf = 0
; Method for doing Van der Waals
vdw-type = PME
vdw-modifier = Potential-Shift
; cut-off lengths
rvdw-switch = 0
rvdw = 1.0
; Apply long range dispersion corrections for Energy and Pressure
DispCorr = EnerPres
; Extension of the potential lookup tables beyond the cut-off
table-extension = 1
; Separate tables between energy group pairs
energygrp-table =
; Spacing for the PME/PPPM FFT grid
fourierspacing = 0.10
; FFT grid size, when a value is 0 fourierspacing will be used
fourier-nx = 0
fourier-ny = 0
fourier-nz = 0
; EWALD/PME/PPPM parameters
pme-order = 6
ewald-rtol = 1e-6
ewald-rtol-lj = 1e-3
lj-pme-comb-rule = Geometric
ewald_geometry = 3d
epsilon-surface = 0
implicit-solvent = no
; OPTIONS FOR WEAK COUPLING ALGORITHMS
; Temperature coupling
tcoupl = No
nsttcouple = -1
nh-chain-length = 10
print-nose-hoover-chain-variables = no
; Groups to couple separately
tc_grps = System
; Time constant (ps) and reference temperature (K)
tau_t = 1.0
ref_t = 300
; pressure coupling
pcoupl = Parrinello-Rahman
pcoupltype = isotropic
nstpcouple = -1
; Time constant (ps), compressibility (1/bar) and reference P (bar)
tau_p = 2
compressibility = 4.5e-05
ref_p = 1.0
; Scaling of reference coordinates, No, All or COM
refcoord-scaling = No
; OPTIONS FOR QMMM calculations
QMMM = no
; Groups treated Quantum Mechanically
QMMM-grps =
; QM method
QMmethod =
; QMMM scheme
QMMMscheme = normal
; QM basisset
QMbasis =
; QM charge
QMcharge =
; QM multiplicity
QMmult =
; Surface Hopping
SH =
; CAS space options
CASorbitals =
CASelectrons =
SAon =
SAoff =
SAsteps =
; Scale factor for MM charges
MMChargeScaleFactor = 1
; SIMULATED ANNEALING
; Type of annealing for each temperature group (no/single/periodic)
annealing =
; Number of time points to use for specifying annealing in each group
annealing-npoints =
; List of times at the annealing points for each group
annealing-time =
; Temp. at each annealing point, for each group.
annealing-temp =
; GENERATE VELOCITIES FOR STARTUP RUN
gen_vel = no
gen-temp = 300
gen-seed = -1
; OPTIONS FOR BONDS
constraints = h-bonds
; Type of constraint algorithm
constraint_algorithm = lincs
; Do not constrain the start configuration
continuation = yes
; Use successive overrelaxation to reduce the number of shake iterations
Shake-SOR = no
; Relative tolerance of shake
shake-tol = 0.0001
; Highest order in the expansion of the constraint coupling matrix
lincs_order = 6
; Number of iterations in the final step of LINCS. 1 is fine for
; normal simulations, but use 2 to conserve energy in NVE runs.
; For energy minimization with constraints it should be 4 to 8.
lincs_iter = 1
; Lincs will write a warning to the stderr if in one step a bond
; rotates over more degrees than
lincs-warnangle = 30
; Convert harmonic bonds to morse potentials
morse = no
; ENERGY GROUP EXCLUSIONS
; Pairs of energy groups for which all non-bonded interactions are excluded
energygrp-excl =
; WALLS
; Number of walls, type, atom types, densities and box-z scale factor for Ewald
nwall = 0
wall-type = 9-3
wall-r-linpot = -1
wall-atomtype =
wall-density =
wall-ewald-zfac = 3
; COM PULLING
pull = no
; AWH biasing
awh = no
; ENFORCED ROTATION
; Enforced rotation: No or Yes
rotation = no
; Group to display and/or manipulate in interactive MD session
IMD-group =
; NMR refinement stuff
; Distance restraints type: No, Simple or Ensemble
disre = No
; Force weighting of pairs in one distance restraint: Conservative or Equal
disre-weighting = Conservative
; Use sqrt of the time averaged times the instantaneous violation
disre-mixed = no
disre-fc = 1000
disre-tau = 0
; Output frequency for pair distances to energy file
nstdisreout = 100
; Orientation restraints: No or Yes
orire = no
; Orientation restraints force constant and tau for time averaging
orire-fc = 0
orire-tau = 0
orire-fitgrp =
; Output frequency for trace(SD) and S to energy file
nstorireout = 100
; Free energy variables
free-energy = yes
couple-moltype = OBM
couple-lambda0 = vdw-q
couple-lambda1 = none
couple-intramol = no
init-lambda = 1
init-lambda-state = -1
delta-lambda = 0
nstdhdl = 25000
fep-lambdas =
mass-lambdas =
coul-lambdas =
vdw-lambdas =
bonded-lambdas =
restraint-lambdas =
temperature-lambdas =
calc-lambda-neighbors = -1
init-lambda-weights =
dhdl-print-energy = no
sc-alpha = 0
sc-power = 1
sc-r-power = 6
sc-sigma = 0.3
sc-coul = no
separate-dhdl-file = yes
dhdl-derivatives = yes
dh_hist_size = 0
dh_hist_spacing = 0.1
; Non-equilibrium MD stuff
acc-grps =
accelerate =
freezegrps =
freezedim =
cos-acceleration = 0
deform =
; simulated tempering variables
simulated-tempering = no
simulated-tempering-scaling = geometric
sim-temp-low = 300
sim-temp-high = 300
; Ion/water position swapping for computational electrophysiology setups
; Swap positions along direction: no, X, Y, Z
swapcoords = no
adress = no
; User defined thingies
user1-grps =
user2-grps =
userint1 = 0
userint2 = 0
userint3 = 0
userint4 = 0
userreal1 = 0
userreal2 = 0
userreal3 = 0
userreal4 = 0
; Electric fields
; Format for electric-field-x, etc. is: four real variables:
; amplitude (V/nm), frequency omega (1/ps), time for the pulse peak (ps),
; and sigma (ps) width of the pulse. Omega = 0 means static field,
; sigma = 0 means no pulse, leaving the field to be a cosine function.
electric-field-x = 0 0 0 0
electric-field-y = 0 0 0 0
electric-field-z = 0 0 0 0