[gmx-users] Relative binding free energy

Mon Mar 14 12:05:32 CET 2016

The minimization crush after 1182 steps like follow

Step= 1116, Dmax= 1.2e-02 nm, Epot= -1.76932e+05 Fmax= 9.54828e+03, atom= 1
Step= 1117, Dmax= 1.4e-02 nm, Epot= -1.77307e+05 Fmax= 2.85691e+04, atom= 8
Step= 1119, Dmax= 8.6e-03 nm, Epot= -1.99060e+05 Fmax= 3.84768e+07, atom= 8
Step= 1124, Dmax= 6.5e-04 nm, Epot= -2.08560e+05 Fmax= 7.94965e+07, atom= 8
Step= 1126, Dmax= 3.9e-04 nm, Epot= -2.34096e+05 Fmax= 2.56256e+08, atom= 8
Step= 1128, Dmax= 2.3e-04 nm, Epot= -2.39440e+05 Fmax= 3.06063e+08, atom= 8
Step= 1130, Dmax= 1.4e-04 nm, Epot= -3.61664e+05 Fmax= 2.64411e+09, atom= 8
Step= 1133, Dmax= 4.2e-05 nm, Epot= -1.12275e+06 Fmax= 6.90055e+10, atom= 8
Step= 1136, Dmax= 1.3e-05 nm, Epot= -1.31351e+06 Fmax= 9.96261e+10, atom= 8
Step= 1138, Dmax= 7.5e-06 nm, Epot= -3.71734e+06 Fmax= 9.66090e+11, atom= 8
Step= 1141, Dmax= 2.3e-06 nm, Epot= -1.52957e+07 Fmax= 1.76138e+13, atom=
11020
Step= 1144, Dmax= 6.8e-07 nm, Epot= -2.62029e+07 Fmax= 5.21932e+13, atom=
81020
Step= 1146, Dmax= 4.1e-07 nm, Epot= -4.13002e+07 Fmax= 1.30309e+14, atom=
11020
Step= 1148, Dmax= 2.4e-07 nm, Epot= -7.52155e+07 Fmax= 4.33870e+14, atom=
11020
Step= 1150, Dmax= 1.5e-07 nm, Epot= -1.08171e+08 Fmax= 8.98648e+14, atom=
11020
Step= 1152, Dmax= 8.8e-08 nm, Epot= -2.33175e+08 Fmax= 4.18302e+15, atom=
11020
Step= 1154, Dmax= 5.3e-08 nm, Epot= -2.60654e+08 Fmax= 5.22788e+15, atom=
11020
Step= 1156, Dmax= 3.2e-08 nm, Epot= -9.62197e+08 Fmax= 7.13107e+16, atom=
11020
Step= 1159, Dmax= 9.5e-09 nm, Epot= -2.35812e+09 Fmax= 4.28405e+17, atom=
11020
Step= 1162, Dmax= 2.8e-09 nm, Epot= -6.67786e+10 Fmax= 3.43602e+20, atom=
11020
Step= 1168, Dmax= 1.1e-10 nm, Epot= -6.70934e+11 Fmax= 3.46861e+22, atom=
11020
Step= 1172, Dmax= 1.6e-11 nm, Epot= -1.02118e+12 Fmax= 8.03509e+22, atom=
81020
Step= 1174, Dmax= 9.6e-12 nm, Epot= -1.98975e+12 Fmax= 3.05062e+23, atom=
11020
Step= 1176, Dmax= 5.8e-12 nm, Epot= -2.58715e+12 Fmax= 5.15738e+23, atom=
11020
Step= 1178, Dmax= 3.5e-12 nm, Epot= -6.80566e+12 Fmax= 3.56885e+24, atom=
11020
Step= 1181, Dmax= 1.0e-12 nm, Epot= -7.62947e+13 Fmax= 4.48513e+26, atom=
81020
Step= 1182, Dmax= 1.2e-12 nm, Epot= -5.58957e+12 Fmax= 2.40735e+24, atom=
11020

As you can see the problem seems to rise in correspondence of the atom 8
(an HG atom). I tried lambda 0 (works), lambda 1 and 2 (do not work) thus
increasing lambda value the simulations crush. I¹m using a single topology
approach to transform a glycine to a D-serine. I checked the topology file
several times and I visualized the gro file too and they seem to e correct.

Thank you in advance for your help

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

On 3/14/16, 12:21 PM, "gromacs.org_gmx-users-bounces at maillist.sys.kth.se
on behalf of Hannes Loeffler"
<gromacs.org_gmx-users-bounces at maillist.sys.kth.se on behalf of
Hannes.Loeffler at stfc.ac.uk> wrote:

>At least in the 4.6 series it used to be the case that when
>couple-moltype was not set (and that's what you want to do) then none
>of the other couple-* parameters ever had any effect.  So there should
>be no need for you to set any of those.
>
>The more important point though would be to provide much more detail
>about the crash during minimization.  When does it happen?  At all
>lambdas, just one?  What was the original structure, what the final
>one? How have you created the topologies, any errors in there? etc.
>
>Cheers,
>Hannes.
>
>
>On Mon, 14 Mar 2016 08:40:41 +0000
>Stefania Evoli <stefania.evoli at kaust.edu.sa> wrote:
>
>> Dear Users,
>>
>> I¹m performing relative binding free energy by using Gromacs 5.0.5.
>> As I understood reading the sections 5.3.4, 6.1 and 7.3.23 of the
>> GROMACS 5.0.5 manual I should avoid to use couple-moltype and
>> couple-lambda0/couple-lambda1 because they would override the A and B
>> states, already defined in the topology file. For this reason I put
>> couple-lambda0 = none, couple-lambda1 = none and couple-intramol =
>> yes to specify I want to modify intramolecular interactions. The
>> problem I¹m having regards the couple-moltype. If I don¹t use it in
>> the mdp file the minimization crashes and if I try to use
>> couple-moltype=none I have the error Œno such a molecule named
>> none¹ (as expected because this parameter is referred to the
>> [moleculetype] section). Could someone that has more experience in
>> this field than me give a look to my mdp file and help me to solve
>> this problem, please. Thank you! NB the following mdp file is an
>> example of my minimization mdp files for lambda=0
>>
>>
>> ; 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           = none
>>
>> couple-lambda1           = none
>>
>> couple-intramol          = yes
>>
>> 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
>>
>>
>>
>> ‹
>> Dr. Stefania Evoli
>> Post-Doctoral Fellow
>> King Abdullah University of Science and Technology
>> Catalysis center - Bldg. 3, 4th floor, 4231WS18
>> Thuwal, Kingdom of Saudi Arabia
>> stefania.evoli at kaust.edu.sa
>>
>>
>>
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>>
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