Hello Justin,

I’m running to the same problem for an AA mutation in a peptide protein binding system.

My .mdp file (taken from http://pmx.mpibpc.mpg.de) is very different from Nuno’s. Also, the distance causing the problem is ridiculously large (1766462.875)!! It happens right after 100 ps.

Interestingly, the same problem happens for a very different system (used in the tutorial: Mutation free energy calculations) if I go beyond 100 ps, (which is the time set in the tutorial).

Any suggestion?

Thank you in advance.

Here is my .mdp file:

;

; VARIOUS PREPROCESSING OPTIONS

title =

include =

define =

; RUN CONTROL PARAMETERS

integrator = md

; Start time and timestep in ps

tinit = 0

dt = 0.002

nsteps = 100000

;200 ps

ld_seed = -1

; For exact run continuation or redoing part of a run

init_step = 0

; mode for center of mass motion removal

comm-mode = Linear

; number of steps for center of mass motion removal

nstcomm = 1

nstcalcenergy = 1

; group(s) for center of mass motion removal

comm-grps =

; ENERGY MINIMIZATION OPTIONS

; Force tolerance and initial step-size

emtol = 100

emstep = 0.01

; Max number of iterations in relax_shells

niter = 0

; Step size (1/ps^2) for minimization of flexible constraints

fcstep = 0

; Frequency of steepest descents steps when doing CG

nstcgsteep = 1000

nbfgscorr = 10

; OUTPUT CONTROL OPTIONS

; Output frequency for coords (x), velocities (v) and forces (f)

nstxout = 0

nstvout = 0

nstfout = 0

; Checkpointing helps you continue after crashes

nstcheckpoint = 1000

; Output frequency for energies to log file and energy file

nstlog = 10000

nstenergy = 100000

; Output frequency and precision for xtc file

nstxtcout = 10000

xtc-precision = 1000

; This selects the subset of atoms for the xtc file. You can

; select multiple groups. By default all atoms will be written.

xtc-grps =

; Selection of energy groups

energygrps =

; NEIGHBORSEARCHING PARAMETERS

; nblist update frequency

cutoff-scheme = verlet

nstlist = 20

; ns algorithm (simple or grid)

ns-type = Grid

; Periodic boundary conditions: xyz (default), no (vacuum)

; or full (infinite systems only)

pbc = xyz

; nblist cut-off

rlist = 1.2

domain-decomposition = no

; OPTIONS FOR ELECTROSTATICS AND VDW

; Method for doing electrostatics

coulombtype = PME

rcoulomb-switch = 0

rcoulomb = 1.1

; Dielectric constant (DC) for cut-off or DC of reaction field

epsilon-r = 1

; Method for doing Van der Waals

vdw-type = switch

; cut-off lengths

rvdw-switch = 1.0

rvdw = 1.1

; Apply long range dispersion corrections for Energy and Pressure

DispCorr = EnerPres

; Extension of the potential lookup tables beyond the cut-off

table-extension = 1

; Spacing for the PME/PPPM FFT grid

fourierspacing = 0.12

; 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 = 4

ewald_rtol = 1e-05

ewald_geometry = 3d

epsilon_surface = 0

optimize_fft = no

; GENERALIZED BORN ELECTROSTATICS

; Algorithm for calculating Born radii

gb_algorithm = Still

; Frequency of calculating the Born radii inside rlist

nstgbradii = 1

; Cutoff for Born radii calculation; the contribution from atoms

; between rlist and rgbradii is updated every nstlist steps

rgbradii = 2

; Salt concentration in M for Generalized Born models

gb_saltconc = 0

; IMPLICIT SOLVENT (for use with Generalized Born electrostatics)

implicit_solvent = No

; OPTIONS FOR WEAK COUPLING ALGORITHMS

; Temperature coupling

tcoupl = v-rescale

; Groups to couple separately

tc-grps = System

; Time constant (ps) and reference temperature (K)

tau-t = 0.1

ref-t = 300

; Pressure coupling

Pcoupl = Parrinello-Rahman

Pcoupltype = Isotropic

; Time constant (ps), compressibility (1/bar) and reference P (bar)

tau-p = 5

compressibility = 4.6E-5

ref-p = 1

; Random seed for Andersen thermostat

andersen_seed = 815131

; SIMULATED ANNEALING

; Type of annealing for each temperature group (no/single/periodic)

annealing = no

; Number of time points to use for specifying annealing in each group

annealing_npoints = 2

; List of times at the annealing points for each group

annealing_time = 0 250

; Temp. at each annealing point, for each group.

annealing_temp = 0 300

; GENERATE VELOCITIES FOR STARTUP RUN

gen-vel = no

gen-temp = 300

gen-seed = 173529

; OPTIONS FOR BONDS

constraints = all-bonds

; Type of constraint algorithm

constraint-algorithm = Lincs

; Do not constrain the start configuration

unconstrained-start = yes

; Use successive overrelaxation to reduce the number of shake iterations

Shake-SOR = no

; Relative tolerance of shake

shake-tol = 1e-04

; 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 = 2

; 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 =

; 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 = Equal

; 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) to energy file

nstorireout = 100

; Dihedral angle restraints: No, Simple or Ensemble

dihre = No

dihre-fc = 1000

dihre-tau = 0

; Output frequency for dihedral values to energy file

nstdihreout = 100

; Free energy control stuff

free_energy = yes

init_lambda = 0

delta_lambda = 0.00002

sc-alpha = 0

sc-sigma = 0.3

refcoord-scaling = all

; Non-equilibrium MD stuff

acc-grps =

accelerate =

freezegrps =

freezedim =

cos-acceleration = 0

; Electric fields

; Format is number of terms (int) and for all terms an amplitude (real)

; and a phase angle (real)

E-x =

E-xt =

E-y =

E-yt =

E-z =

E-zt =

; User defined thingies

user1-grps =

user2-grps =

userint1 = 0

userint2 = 0

userint3 = 0

userint4 = 0

userreal1 = 0

userreal2 = 0

userreal3 = 0

userreal4 = 0