[gmx-users] Relative binding free energy
Hannes Loeffler
Hannes.Loeffler at stfc.ac.uk
Mon Mar 14 12:35:38 CET 2016
How does the final structure for lambda=0 minimisation look like? This
may give you a hint as to what is wrong.
What exactly does "do not work" mean? That's not very descriptive...
It may help a lot to actually post the relevant A and B columns from
your topologies. Single topology means in your case that you map both
backbones plus one hydrogen onto each other. The other hydrogen (the
right one hopefully!) maps onto the C-beta of serine. The remaining
atoms need to be defined as dummy atoms in the glycine state. Have you
had a look into pmx to have this done for you?
On Mon, 14 Mar 2016 11:05:14 +0000
Stefania Evoli <stefania.evoli at kaust.edu.sa> wrote:
> 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
> >>
> >>
> >>
> >> ________________________________
> >>
> >> This message and its contents including attachments are intended
> >> solely for the original recipient. If you are not the intended
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> >
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