[gmx-users] energy.edr retrieves deltaG = 0 KJ/mol using g_lie

Justin A. Lemkul jalemkul at vt.edu
Mon May 24 13:02:22 CEST 2010



Hassan Shallal wrote:
> Dear Justin, Thanks alot for the feedback, I forgot to set the Clj and the
> Cqq and the ligand options for g_lie, I set them and I got the energy
> calculated and it is reasonable value. I am waiting to do the same thing for
> the whole complex (protein, ligand and sol) and get an estimate of the free
> energy of binding...
> 
> I still have a question for you and for other users who have done similar
> free energy calculations using g_lie, do the parameter file I include in this
> message seem fine? is there something that I missed and you or anyone else
> thinks I should have included?
> 

The parameters you choose are based on the goals you should be setting at the 
outset of the simulation.  Using plain cutoffs is required for using g_lie, but 
is otherwise discouraged due to artefacts.  The parameters are syntactically 
correct, no glaring errors, but whether or not they accomplish what you need is 
something only you know.

-Justin

> Once again thanks alot for the feedback
> 
> The .mdp file:
> 
> ;RUN CONTROL PARAMETERS = integrator          =  md       ; production tinit
> =  0        ; starting time for your run (only makes sense for integrators
> md, sd and bd) dt                  =  0.002    ; ps ! nsteps              =
> 2500000  ; total 5 ns. nstcomm             =  1        ; frequency for center
> of mass motion removal ;OUTPUT FREQUENCY OPRIONS FOR COORDINATES, VELOCITIES,
> AND FORCES = nstxout                  = 1000    ; frequency to write
> coordinates to output trajectory file, the last coordinates are always
> written nstvout                  = 1000    ; frequency to write velocities to
> output trajectory, the last velocities are always written nstfout
> = 0    ; frequency to write forces to output trajectory. ;OUTPUT FREQUENCY
> OPRIONS FOR ENERGIES = nstlog                   = 2500 ; frequency to write
> energies to log file, the last energies are always written nstenergy
> = 1000 ; frequency to write energies to energy file, the last energies are
> always written ;NEIGHBOR SEARCHING PARAMETERS = nstlist             =  10
> ; neighbor list update frequency ns_type             =  grid     ; ns
> algorithm (simple or grid) pbc                 =  xyz      ; periodic
> boundary conditions (xyz or none) rlist               =  1        ; cut-off
> distance of the short-range neighbor list (nm) domain-decomposition = no 
> ;OUTPUT FREQUENCY AND PRESISION FOR XTC FILES = nstxtcout                =
> 5000  ; frequency to write coordinates to xtc trajectory (STEPS) 
> xtc-precision            = 1000  ; precision to write to xtc trajectory 
> energygrps               = SOL UNK ;OPTIONS FOR ELECTROSTATIC AND VDW = 
> coulombtype         =  Cut-off  ; method of doing electrostatics (Twin range
> cut-off's with neighborlist cut-off rlist and Coulomb cut-off rcoulomb where
> rcoulomb ? rlist.) rcoulomb_switch     =  0        ; where to start switching
> the Coulomb potential (nm) rcoulomb            =  1        ; distance for
> Coulomb cut-off (nm) epsilon_r           =  1        ; the relative
> dielectric constant (1 or zero, if zero, means infinity) vdwtype
> =  Cut-off  ; method of doing VDW (Twin range cut-off's with neighbor list
> cut-off rlist and VdW cut-off rvdw, where rvdw ? rlist.) rvdw
> =  1        ; distance for LJ or Buckingham cut-off (nm) DispCorr
> =  no       ; Don't apply long range dispersion corrections for Energy and
> Pressure ;OPTIONS FOR TEMPERATURE COUPLING = Tcoupl              =  v-rescale
>  tau_t               =  0.1        ; time constant for coupling in ps (one
> for each group in tc grps), 0 means no temperature coupling tc_grps
> =  System ref_t               =  298.15 ;OPTIONS FOR PRESSURE COUPLING Pcoupl
> = no pcoupltype               = isotropic   ; Isotropic pressure coupling
> with time constant tau_p                    = 0.5         ; time constant for
> coupling in ps compressibility          = 4.5e-05     ; compressibility for
> water at 1 atm and 300 K ref_p                    = 1.0
> 
> ________________________________
> 
> From: gmx-users-bounces at gromacs.org on behalf of Justin A. Lemkul Sent: Sun
> 5/23/2010 8:54 PM To: Discussion list for GROMACS users Subject: Re:
> [gmx-users] energy.edr retrieves deltaG = 0 KJ/mol using g_lie
> 
> 
> 
> 
> 
> Hassan Shallal wrote:
>> Dear Gromacs users,
>> 
>> I ran a production MD simulation on a ligand in a water box. I used NVT 
>> with coloumb and vdw cut-offs and avoided using PME. I analyzed the .edr 
>> file using g_lie after the simulation was finished, I found that at all the
>> time steps, the energy was 0 KJ/mol, is that normal? How come the energy of
>> the system is 0? ' I am including both the simulation mdp file and the
>> output of g_lie for inspection...
>> 
> 
> What was your g_lie command?  The default values of -Elj and -Eqq are zero. 
> Based on your energygrps (SOL and UNK), you are inherently defining the 
> interactions between the solvent and UNK as zero unless you are setting some 
> other value.
> 
> -Justin
> 
>> I would appreciate if I could get any feedback about the reasons for this
>> problem. Regards
>> 
>> Hassan Shallal University of the Pacific Stockton, CA 95211
>> 
>> The mdb file:
>> 
>> ------------------------------------------------------------------------------------------------------------------------------------------------------------------
>>  ;RUN CONTROL PARAMETERS = integrator          =  md       ; production 
>> tinit               =  0        ; starting time for your run (only makes 
>> sense for integrators md, sd and bd) dt                  =  0.002    ; ps !
>>  nsteps              =  2500000  ; total 5 ns. nstcomm             =  1
>> ; frequency for center of mass motion removal ;OUTPUT FREQUENCY OPRIONS FOR
>> COORDINATES, VELOCITIES, AND FORCES = (because this is equilibration, we
>> don't want to waste hard disk storgae space) nstxout                  =
>> 1000    ; frequency to write coordinates to output trajectory file, the
>> last coordinates are always written nstvout                  = 1000    ;
>> frequency to write velocities to output trajectory, the last velocities are
>> always written nstfout                  = 0    ; frequency to write forces
>> to output trajectory. ;OUTPUT FREQUENCY OPRIONS FOR ENERGIES = nstlog
>> = 2500 ; frequency to write energies to log file, the last energies are
>> always written nstenergy                = 1000 ; frequency to write
>> energies to energy file, the last energies are always written ;NEIGHBOR
>> SEARCHING PARAMETERS = nstlist             =  10       ; neighbor list
>> update frequency ns_type             =  grid     ; ns algorithm (simple or
>> grid) pbc                 =  xyz      ; periodic boundary conditions (xyz
>> or none) rlist               =  1        ; cut-off distance of the
>> short-range neighbor list (nm) domain-decomposition = no ;OUTPUT FREQUENCY
>> AND PRESISION FOR XTC FILES = nstxtcout                = 5000  ; frequency
>> to write coordinates to xtc trajectory (STEPS) xtc-precision            =
>> 1000  ; precision to write to xtc trajectory energygrps               = SOL
>> UNK ;OPTIONS FOR ELECTROSTATIC AND VDW = coulombtype         =  Cut-off  ;
>> method of doing electrostatics (Twin range cut-off's with neighborlist
>> cut-off rlist and Coulomb cut-off rcoulomb, where rcoulomb ? rlist.) 
>> rcoulomb_switch     =  0        ; where to start switching the Coulomb 
>> potential (nm) rcoulomb            =  1        ; distance for Coulomb
>> cut-off (nm) epsilon_r           =  1        ; the relative dielectric
>> constant (1 or zero, if zero, means infinity) vdwtype             =
>> Cut-off  ; method of doing VDW (Twin range cut-off's with neighbor list
>> cut-off rlist and VdW cut-off rvdw, where rvdw ? rlist.) rvdw
>> =  1        ; distance for LJ or Buckingham cut-off (nm) DispCorr
>> =  no       ; Don't apply long range dispersion corrections for Energy and
>> Pressure ;OPTIONS FOR TEMPERATURE COUPLING = Tcoupl              =
>> v-rescale tau_t               =  0.1            ; time constant for
>> coupling in ps (one for each group in tc grps), 0 means no temperature
>> coupling tc_grps             =  System         ; to avoid hot solvent cold
>> solute situation ref_t               =  298.15 ;OPTIONS FOR PRESSURE
>> COUPLING Pcoupl                   = no pcoupltype               = isotropic
>> ; Isotropic pressure coupling with time constant tau_p                    =
>> 0.5         ; time constant for coupling in ps compressibility          =
>> 4.5e-05     ; compressibility for water at 1 atm and 300 K ref_p
>> = 1.0 
>> -------------------------------------------------------------------------------------------------------------------------------------------------------------------
>>  The .xvg g_lie output file: 
>> ------------------------------------------------------------------------------------------------------------------------------------------------------------------
>>  # This file was created Fri May 21 17:21:18 2010 # by the following
>> command: # g_lie -f 4_pr_NVT.edr -o 4_pr_NVT.xvg # # g_lie is part of G R O
>> M A C S: # # Grunge ROck MAChoS # @    title "LIE free energy estimate" @
>> xaxis  label "Time (ps)" @    yaxis  label "DGbind (kJ/mol)" @TYPE xy 0
>> 0 2           0 4           0 6           0 8           0 10           0 12
>> 0 14           0 16           0 18           0 20           0 22
>> 0 all the way until 5000           0 0           0 
>> ------------------------------------------------------------------------------------------------------------
>> 
>> 
> 
> -- ========================================
> 
> Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee 
> Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu |
> (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
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-- 
========================================

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

========================================



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