[gmx-users] Relative binding free energy

Stefania Evoli stefania.evoli at kaust.edu.sa
Thu Feb 18 12:32:20 CET 2016


Dear users,

I’m performing relative binding free energy calculation in Gromacs 5.0.5 of two amino acids: Alanine and Glycine. After the minimization phase the simulations crush giving me output file like 'step***.pdb' and the error is

'Fatal error:

Too many LINCS warnings (1000)

If you know what you are doing you can adjust the lincs warning threshold in your mdp file

or set the environment variable GMX_MAXCONSTRWARN to -1,

but normally it is better to fix the problem’.

Probably the problem raises when the OH appear and binds the CB. I’m using the soft-core potentials and the steep integrator as you can see in the following mdp file


; RUN CONTROL PARAMETERS

integrator               = steep

; Start time and timestep in ps

tinit                    = 0

dt                       = 0.002

nsteps                   = 2500

; mode for center of mass motion removal

comm-mode                = Linear

; number of steps for center of mass motion removal

nstcomm                  = 100 ; must be equal or larger than calcenergy

nstcalcenergy            = 100 ; Default


; CUTOFF SCHEME (default = verlet now)

cutoff-scheme           = group


; ENERGY MINIMIZATION OPTIONS

; Force tolerance and initial step-size

emtol                    = 100

emstep                   = 0.01

; Max number of iterations in relax_shells

niter                    = 20

; 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, they are always included now

; Output frequency for energies to log file and energy file

nstlog                   = 100

nstenergy                = 100

; Output frequency and precision for xtc file

nstxout-compressed                = 0

compressed-x-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

nstlist                  = 10

; 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


; OPTIONS FOR ELECTROSTATICS AND VDW

; Method for doing electrostatics

coulombtype              = pme

rcoulomb-switch          = 0

rcoulomb                 = 1.2

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

; Method for doing Van der Waals

vdw-type                 = Cut-off

vdw-modifier             = Potential-switch

; cut-off lengths

rvdw-switch              = 0.9

rvdw                     = 1.0

; Apply long range dispersion corrections for Energy and Pressure

DispCorr                 = AllEnerPres

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

; 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-06

ewald_geometry           = 3d

epsilon_surface          = 0


; OPTIONS FOR WEAK COUPLING ALGORITHMS

; Temperature coupling

Tcoupl                   = no

; Groups to couple separately

tc-grps                  = System

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

tau_t                    = 2.0

ref_t                    = 298.15

; Pressure coupling

Pcoupl                   = no

Pcoupltype               = isotropic

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

tau_p                    = 1

compressibility          = 4.5e-5

ref_p                    = 1.01325


; GENERATE VELOCITIES FOR STARTUP RUN

gen_vel                  = yes

gen_temp                 = 298.15

gen_seed                 = 1993


; OPTIONS FOR BONDS

constraints              = hbonds

; Type of constraint algorithm

constraint-algorithm     = Lincs

; Do not constrain the start configuration

continuation      = no

; 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              = 12

; 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 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           =


; Free energy control stuff

free-energy              = yes

init_lambda_state        = 0

fep_lambdas              = 0.0 0.25 0.5 0.75 1.0 1.00 1.0 1.0 1.0 1.0 1.0 1.0 1.0  1.0 1.0  1.0 1.0  1.0 1.0  1.0

vdw_lambdas              = 0.0 0.00 0.0 0.00 0.0 0.05 0.1 0.2 0.3 0.4 0.5 0.6 0.65 0.7 0.75 0.8 0.85 0.9 0.95 1.0

;couple-moltype           = LIG

;couple-lambda0           = vdw-q

;couple-lambda1           = none

;couple-intramol          = no

sc-alpha                 = 0.5

sc-sigma                 = 0.3

sc-power                 = 1.0

sc-r-power               = 6

sc-coul                  = no

nstdhdl                  = 100

calc-lambda-neighbors    = -1


I tried to modify the integrator or the soft-core parameters but nothing changed. Did someone have a problem like that? How is it possible to solve it?


Thanks,

Stefania

—
Dr. Stefania Evoli
Post-Doctoral Fellow
King Abdullah University of Science and Technology
Catalysis center - Bldg. 3, 4th floor, 4231–WS18
Thuwal, Kingdom of Saudi Arabia
stefania.evoli at kaust.edu.sa



________________________________

This message and its contents including attachments are intended solely for the original recipient. If you are not the intended recipient or have received this message in error, please notify me immediately and delete this message from your computer system. Any unauthorized use or distribution is prohibited. Please consider the environment before printing this email.


More information about the gromacs.org_gmx-users mailing list