[gmx-users] topology and parameter set up

Jennifer Vo quyviolet at gmail.com
Mon Feb 2 14:20:53 CET 2015


Dear Justin,
Many thanks for your help. My em.mdp is
integrator      = steep
emtol           = 100.0
emstep          = 0.01
nsteps          = 100000
coulombtype     = PME
pbc             = xyz

My nvt.mdp is
title       = Protein-ligand complex NVT equilibration
define      = -DPOSRES -DPOSRES_LIG ; position restrain the protein and
ligand
; Run parameters
integrator  = md        ; leap-frog integrator
nsteps      = 50000     ; 2 * 50000 = 100 ps
dt          = 0.002     ; 2 fs
; Output control
nstxout     = 500       ; save coordinates every 1.0 ps
nstvout     = 500       ; save velocities every 1.0 ps
nstenergy   = 500       ; save energies every 1.0 ps
nstlog      = 500       ; update log file every 1.0 ps
energygrps  = Protein NPD
; Bond parameters
continuation    = no            ; first dynamics run
constraint_algorithm = lincs    ; holonomic constraints
constraints     = hbonds     ; all bonds (even heavy atom-H bonds)
constrained
lincs_iter      = 1             ; accuracy of LINCS
lincs_order     = 4             ; also related to accuracy
; Neighborsearching
cutoff-scheme   = Verlet
ns_type         = grid      ; search neighboring grid cells
nstlist         = 10        ; 20 fs, largely irrelevant with Verlet
rcoulomb        = 1.4       ; short-range electrostatic cutoff (in nm)
rvdw            = 1.4       ; short-range van der Waals cutoff (in nm)
; Electrostatics
coulombtype     = PME       ; Particle Mesh Ewald for long-range
electrostatics
pme_order       = 4         ; cubic interpolation
fourierspacing  = 0.16      ; grid spacing for FFT
; Temperature coupling
tcoupl      = V-rescale                     ; modified Berendsen thermostat
tc-grps     = Protein_NPD Water_and_ions    ; two coupling groups - more
accurate
tau_t       = 0.1   0.1                     ; time constant, in ps
ref_t       = 300   300                     ; reference temperature, one
for each group, in K
; Pressure coupling
pcoupl      = no        ; no pressure coupling in NVT
; Periodic boundary conditions
pbc         = xyz       ; 3-D PBC
; Dispersion correction
DispCorr    = EnerPres  ; account for cut-off vdW scheme
; Velocity generation
gen_vel     = yes       ; assign velocities from Maxwell distribution
gen_temp    = 300       ; temperature for Maxwell distribution
gen_seed    = -1        ; generate a random seed

It generated no error in the log file. This is em.log
Steepest Descents converged to Fmax < 100 in 10536 steps
Potential Energy  = -2.1753502e+06
Maximum force     =  8.4056786e+01 on atom 100002
Norm of force     =  4.0102091e+00

For the NPT.mdp, since I have got error from the previous run, so I tried
commenting out the neighborsearching part to take the default number and
there is still error as the previous email.

Regarding the coordinates, I merged 2 coordinate files into 1 file as your
tutorial about Protein-Ligand Simulation (
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/complex/02_topology.html)
and
run a genconf to renumber the system, editconf to create the cubic box and
genbox to solvate the system. Then I add 24 NA since the charge of the
whole system is -24.

I don't know which step is a possible cause to the error.
Regards,
Jennifer


On Mon, Feb 2, 2015 at 1:57 PM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 2/2/15 6:37 AM, Jennifer Vo wrote:
>
>> Dear Experts,
>> I am facing the problem of simulation of protein - ligand complex using
>> amber99sb force field.
>> Since I created a topol.top for the system
>>
>> ; Include forcefield parameters
>> #include "amber99sb.ff/forcefield.itp"
>> [ atomtypes ]
>> ;name   bond_type     mass     charge   ptype   sigma         epsilon
>> Amb
>>   CA       CA          0.00000  0.00000   A     3.39967e-01   3.59824e-01
>> ;
>> 1.91  0.0860
>>   H4       H4          0.00000  0.00000   A     2.51055e-01   6.27600e-02
>> ;
>> 1.41  0.0150
>>   HA       HA          0.00000  0.00000   A     2.59964e-01   6.27600e-02
>> ;
>> 1.46  0.0150
>>   C        C           0.00000  0.00000   A     3.39967e-01   3.59824e-01
>> ;
>> 1.91  0.0860
>>   O        O           0.00000  0.00000   A     2.95992e-01   8.78640e-01
>> ;
>> 1.66  0.2100
>>   N        N           0.00000  0.00000   A     3.25000e-01   7.11280e-01
>> ;
>> 1.82  0.1700
>>   H        H           0.00000  0.00000   A     1.06908e-01   6.56888e-02
>> ;
>> 0.60 0.0157
>>   N*       N*          0.00000  0.00000   A     3.25000e-01   7.11280e-01
>> ;
>> 1.82  0.1700
>>   CT       CT          0.00000  0.00000   A     3.39967e-01   4.57730e-01
>> ;
>> 1.91  0.1094
>>   H2       H2          0.00000  0.00000   A     2.29317e-01   6.56888e-02
>> ;
>> 1.29  0.0157
>>   H1       H1          0.00000  0.00000   A     2.47135e-01   6.56888e-02
>> ;
>> 1.39  0.0157
>>   OH       OH          0.00000  0.00000   A     3.06647e-01   8.80314e-01
>> ;
>> 1.72  0.2104
>>   HO       HO          0.00000  0.00000   A     0.00000e+00   0.00000e+00
>> ;
>> 0.00  0.0000
>>   OS       OS          0.00000  0.00000   A     3.00001e-01   7.11280e-01
>> ;
>> 1.68 0.1700
>>   P        P           0.00000  0.00000   A     3.74177e-01   8.36800e-01
>> ;
>> 2.10  0.2000
>>   O2       O2          0.00000  0.00000   A     2.95992e-01   8.78640e-01
>> ;
>> 1.66  0.2100
>>   CK       CK          0.00000  0.00000   A     3.39967e-01   3.59824e-01
>> ;
>> 1.91  0.0860
>>   H5       H5          0.00000  0.00000   A     2.42146e-01   6.27600e-02
>> ;
>> 1.36  0.0150
>>   NB       NB          0.00000  0.00000   A     3.25000e-01   7.11280e-01
>> ;
>> 1.82  0.1700
>>   CB       CB          0.00000  0.00000   A     3.39967e-01   3.59824e-01
>> ;
>> 1.91  0.0860
>>   N2       N2          0.00000  0.00000   A     3.25000e-01   7.11280e-01
>> ;
>> 1.82  0.1700
>>   NC       NC          0.00000  0.00000   A     3.25000e-01   7.11280e-01
>> ;
>> 1.82  0.1700
>>   CQ       CQ          0.00000  0.00000   A     3.39967e-01   3.59824e-01
>> ;
>> 1.91  0.0860
>> ; Include chain topologies
>> #include "A.itp"
>> ; Include Position restraint file
>> #ifdef POSRES
>> #include "posre_A.itp"
>> #endif
>> ; Include chain topologies
>> #include "B.itp"
>> ; Include Position restraint file
>> #ifdef POSRES
>> #include "posre_B.itp"
>> #endif
>> ; Include custom ligand topologies
>> #include "npd.itp"
>> ; Ligand position restraints
>> #ifdef POSRES_LIG
>> #include "posre_npd.itp"
>> #endif
>>
>> ; Include water topology
>> #include "amber99sb.ff/tip3p.itp"
>>
>> #ifdef POSRES_WATER
>> ; Position restraint for each water oxygen
>> [ position_restraints ]
>> ;  i funct       fcx        fcy        fcz
>>     1    1       1000       1000       1000
>> #endif
>> ; Include generic ion topology
>> #include "amber99sb.ff/ions.itp"
>>
>> [ system ]
>> ; Name
>> system in water
>> [ molecules ]
>> ; Compound        #mols
>> A                     1
>> B                     1
>> NPD                   1
>> SOL               42322
>> NA                   24
>>
>> The Protein and the Ligand were under energy minimization and a short MD
>> separatedly to be sure there is no problem with the topology. But when I
>> merge two topol.top from protein and from ligand, the error came at NPT
>> step after successfully energy minimization and NVT
>> "This is likely either a 1,4 interaction, or a listed interaction inside a
>> smaller molecule you are decoupling during a free energy calculation.
>> Since
>> interactions at distances beyond the table cannot be computed, they are
>> skipped until they are inside the table limit again. You will only see
>> this
>> message once, even if it occurs for several interactions.
>> IMPORTANT: This should not happen in a stable simulation, so there is
>> probably something wrong with your system. Only change the table-extension
>> distance in the mdp file if you are really sure that is the reason."
>>
>> This is NPT.mdp
>> title           = system in water
>> define          = -DPOSRES -DPOSRES_LIG ; position restrain the protein
>> ; Run parameters
>> integrator      = md            ; leap-frog integrator
>> nsteps          = 500000                ; 2 * 500000 = 1000 ps, 1 ns
>> dt                  = 0.002             ; 2 fs
>> ; Output control
>> nstxout         = 5000          ; save coordinates every 1.0 ps
>> nstvout         = 5000          ; save velocities every 1.0 ps
>> nstenergy       = 500           ; save energies every 1.0 ps
>> nstlog          = 500           ; update log file every 1.0 ps
>> energygrps      = Protein NPD
>> ; Bond parameters
>> continuation            = yes           ; Restarting after NVT
>> constraint_algorithm    = lincs     ; holonomic constraints
>> constraints             = all-bonds ; all bonds (even heavy atom-H bonds)
>> constrained
>> lincs_iter              = 1             ; accuracy of LINCS
>> lincs_order             = 4             ; also related to accuracy
>>
>> ; Neighborsearching
>> ;ns_type     = grid              ; search neighboring grid cels
>> ;nstlist     = 5                 ; 10 fs
>> ;rlist       = 1.4               ; short-range neighborlist cutoff (in nm)
>> ;rcoulomb    = 1.4               ; short-range electrostatic cutoff (in
>> nm)
>> ;rvdw        = 1.4               ; short-range van der Waals cutoff (in
>> nm)
>>
>>
> You have commented out the most critical elements of the input file.  You
> need to specify your nonbonded settings, otherwise you're relying solely on
> defaults, which may or may not be right for the force field you're using.
>
>
>  ; Electrostatics
>> coulombtype         = PME               ; Particle Mesh Ewald for
>> long-range electrostatics
>> pme_order           = 4             ; cubic interpolation
>> fourierspacing  = 0.16          ; grid spacing for FFT
>>
>> ; Temperature coupling is on
>> tcoupl          = V-rescale                 ; modified Berendsen
>> thermostat
>> tc-grps         = Protein_NPD Water_and_ions    ; two coupling groups -
>> more accurate
>> tau_t           = 0.1     0.1           ; time constant, in ps
>> ref_t           = 300     300           ; reference temperature, one for
>> each group, in K
>> ; Pressure coupling is on
>> pcoupl                  = Berendsen         ; Pressure coupling on in NPT
>> pcoupltype              = isotropic                 ; uniform scaling of
>> box vectors
>> tau_p                   = 2.0                       ; time constant, in ps
>> ref_p                   = 1.0                       ; reference pressure,
>> in bar
>> compressibility     = 4.5e-5                ; isothermal compressibility
>> of
>> water, bar^-1
>> refcoord_scaling    = com
>> ; Periodic boundary conditions
>> pbc             = xyz           ; 3-D PBC
>> ; Dispersion correction
>> DispCorr        = EnerPres      ; account for cut-off vdW scheme
>> ; Velocity generation
>> gen_vel         = no            ; Velocity generation is off
>>
>>
> Given that you're not generating velocities, presumably you're picking up
> from a previous run?  What were its settings and ensemble?  Was it stable?
>
> Also be sure to check the merged coordinates and make sure energy
> minimization was sensible.
>
> -Justin
>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==================================================
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