# [gmx-users] deltaG from PMF

Steven Neumann s.neumann08 at gmail.com
Fri Aug 24 14:58:52 CEST 2012

```I did g_wham calculation as you suggested for:
10-30 ns
30-50 ns
10-50 ns

In some cases of PMF curves the drift is 0.3 kcal/mol but in some
cases it is over 1.5 kcal/mol so huge drifts. In terms of huge drifts
what would you suggest ?

Steven

On Tue, Aug 21, 2012 at 5:48 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>
> On 8/21/12 12:46 PM, Steven Neumann wrote:
>>
>> Thanks Thomas.
>> Justin, could you please comment on this?
>>
>
> I agree with everything Thomas has said.  There's not really anything to
> say.
>
> -Justin
>
>
>> Steven
>>
>> On Tue, Aug 21, 2012 at 5:37 PM, Thomas Schlesier <schlesi at uni-mainz.de>
>> wrote:
>>>
>>> Am 21.08.2012 18:22, schrieb gmx-users-request at gromacs.org:
>>>>
>>>>
>>>> On Tue, Aug 21, 2012 at 4:49 PM, Thomas Schlesier<schlesi at uni-mainz.de>
>>>> wrote:
>>>>>
>>>>>
>>>>>> Since your simulations of the individual windows are about 50 ns, you
>>>>>> could
>>>>>> first dismiss the first 10 ns for equilibration, and then perform the
>>>>>> WHAM
>>>>>> analysis for 10-30 ns and 30-50 ns. If everything is fine, you should
>>>>>> see no
>>>>>> drift.
>>>>>> If you want to have more data for the analysis you could also use 5ns
>>>>>> ;
>>>>>> 5-27.5ns and 27.5-50ns.
>>>>>>
>>>>>>  From the PMF it seems that the equilibrium state should be around 0.6
>>>>>> nm. To
>>>>>> be sure, you can perform a normal simulation (without any restraints)
>>>>>> from
>>>>>> you initial starting window (~0.4nm) and a window near the minima
>>>>>> (~0.6nm).
>>>>>> Then after the equilibration phase, look at the distribution of the
>>>>>> distance
>>>>>> along the reaction coordinate. If in both cases the maximum is at
>>>>>> ~0.6nm,
>>>>>> this should be the 'true' equilibrium state of the system (instead of
>>>>>> the
>>>>>> first window of the PMF calculation) and i would measure \Delta G from
>>>>>> this
>>>>>> point.
>>>>>>
>>>>>> Greetings
>>>>>> Thomas
>>>>
>>>>
>>>>
>>>>
>>>> Thanks Thomas for this but finally I realised that my first
>>>> configuration corresponds to 0.6 nm which is the minima so I take the
>>>> free energy difference based on this value and plateau.
>>>>
>>>> I want also to calculate error bars. Would you do this:
>>>>
>>>> Final PMF curve for 10-50 ns
>>>>
>>>> Error bars from:
>>>> g_wham -b 30000 -e 40000
>>>>
>>>> g_wham -b 50000 -e 60000
>>>>
>>>
>>> Think this approach would be good to see if you have any drifts.
>>> But for error bars there is something implemented in 'g_wham'. But i
>>> never
>>> used it, since for my system umbrella sampling is not really applicable,
>>> only TI. So i can't comment on it, if there is anything one should be
>>> aware
>>> of, or similar. But 'g_wham -h' prints some info about how to use the
>>> error
>>> analysis
>>> Greetings
>>> Thomas
>>>
>>>
>>>
>>>>
>>>>
>>>> Steven
>>>>
>>>>
>>>>>>
>>>>>>
>>>>>> Am 21.08.2012 17:25, schriebgmx-users-request at gromacs.org:
>>>>>>
>>>>>>
>>>>>>>> On Tue, Aug 21, 2012 at 4:21 PM, Justin Lemkul<jalemkul at vt.edu>
>>>>>>>> wrote:
>>>>>>>
>>>>>>>
>>>>>>>>>>
>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>> On 8/21/12 11:18 AM, Steven Neumann wrote:
>>>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>> On Tue, Aug 21, 2012 at 4:13 PM, Justin
>>>>>>>>>>>>>>>> Lemkul<jalemkul at vt.edu>
>>>>>>>>>>>>>>>> wrote:
>>>>>>>>>
>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>> On 8/21/12 11:09 AM, Steven Neumann wrote:
>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>> On Tue, Aug 21, 2012 at 3:48 PM, Justin
>>>>>>>>>>>>>>>>>>>>>>>> Lemkul<jalemkul at vt.edu>
>>>>>>>>>>>>>>>>>>>>>>>> wrote:
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>> On 8/21/12 10:42 AM, Steven Neumann wrote:
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> Please see the example of the plot from US
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> simulations and
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> WHAM:
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> http://speedy.sh/Ecr3A/PMF.JPG
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> First grompp of frame 0 corresponds to 0.8
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nm
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> - this is what
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> was shown
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> by grompp at the end.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> The mdp file:
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ; Run parameters
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> define      = -DPOSRES_T
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> integrator  = md        ; leap-frog
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> integrator
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nsteps      = 25000000     ; 100ns
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> dt          = 0.002     ; 2 fs
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> tinit       = 0
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nstcomm     = 10
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ; Output control
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nstxout     = 0       ; save coordinates
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> every 100 ps
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nstvout     = 0       ; save velocities
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> every
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nstxtcout   = 50000        ; every 10 ps
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nstenergy   = 1000
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ; Bond parameters
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> continuation    = no           ; first
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> dynamics run
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> constraint_algorithm = lincs    ; holonomic
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> constraints
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> constraints     = all-bonds     ; all bonds
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> (even heavy atom-H
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> bonds)
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> constrained
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ; Neighborsearching
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ns_type     = grid      ; search neighboring
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> grid cells
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nstlist     = 5         ; 10 fs
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> vdwtype     = Switch
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> rvdw-switch = 1.0
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> rlist       = 1.4       ; short-range
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> neighborlist cutoff (in
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nm)
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> rcoulomb    = 1.4       ; short-range
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> electrostatic cutoff (in
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nm)
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> rvdw        = 1.2       ; short-range van
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> der
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> Waals cutoff (in
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nm)
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ewald_rtol  = 1e-5      ; relative strenght
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> of the
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> Ewald-shifted
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> potential rcoulomb
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ; Electrostatics
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> coulombtype     = PME       ; Particle Mesh
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> Ewald for
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> long-range
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> electrostatics
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pme_order       = 4         ; cubic
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> interpolation
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> fourierspacing  = 0.12      ; grid spacing
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> for FFT
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> fourier_nx      = 0
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> fourier_ny      = 0
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> fourier_nz      = 0
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> optimize_fft    = yes
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ; Temperature coupling is on
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> tcoupl      = V-rescale
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ;
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> modified
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> Berendsen
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> thermostat
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> tc_grps     = Protein LIG_Water_and_ions   ;
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> two coupling
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> groups -
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> more
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> accurate
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> tau_t       = 0.1   0.1
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ;
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> time constant,
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> in ps
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ref_t       = 318   318
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ;
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> reference
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> temperature,
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> one for each group, in K
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ; Pressure coupling is on
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pcoupl      = Parrinello-Rahman
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ;
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pressure
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> coupling is on
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> for
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> 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
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ; 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    = 318       ; temperature for
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> Maxwell distribution
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> gen_seed    = -1        ; generate a random
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> seed
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ; These options remove COM motion of the
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> system
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ; Pull code
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull            = umbrella
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_geometry   = distance
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_dim        = N N Y
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_start      = yes
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_ngroups    = 1
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_group0     = Protein
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_group1     = LIG
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_init1      = 0
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_rate1      = 0.0
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_k1         = 500      ; kJ mol^-1
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> nm^-2
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_nstxout    = 1000    ; every 2 ps
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> pull_nstfout    = 1000      ; every 2 ps
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>> Based on these settings you're allowing grompp
>>>>>>>>>>>>>>>>>>>>>>>>>>>> to
>>>>>>>>>>>>>>>>>>>>>>>>>>>> set the
>>>>>>>>>>>>>>>>>>>>>>>>>>>> reference
>>>>>>>>>>>>>>>>>>>>>>>>>>>> distance
>>>>>>>>>>>>>>>>>>>>>>>>>>>> to whatever it finds in the coordinate file.  It
>>>>>>>>>>>>>>>>>>>>>>>>>>>> seems clear to
>>>>>>>>>>>>>>>>>>>>>>>>>>>> me that
>>>>>>>>>>>>>>>>>>>>>>>>>>>> the
>>>>>>>>>>>>>>>>>>>>>>>>>>>> sampling indicates what I said before - you have
>>>>>>>>>>>>>>>>>>>>>>>>>>>> an energy
>>>>>>>>>>>>>>>>>>>>>>>>>>>> minimum
>>>>>>>>>>>>>>>>>>>>>>>>>>>> somewhere
>>>>>>>>>>>>>>>>>>>>>>>>>>>> other than where you "started" with.  What that
>>>>>>>>>>>>>>>>>>>>>>>>>>>> state
>>>>>>>>>>>>>>>>>>>>>>>>>>>> corresponds to
>>>>>>>>>>>>>>>>>>>>>>>>>>>> relative to what you think is going on is for
>>>>>>>>>>>>>>>>>>>>>>>>>>>> you
>>>>>>>>>>>>>>>>>>>>>>>>>>>> to decide
>>>>>>>>>>>>>>>>>>>>>>>>>>>> based on
>>>>>>>>>>>>>>>>>>>>>>>>>>>> the
>>>>>>>>>>>>>>>>>>>>>>>>>>>> nature of your system.  Whatever is occurring at
>>>>>>>>>>>>>>>>>>>>>>>>>>>> 0.6 nm of COM
>>>>>>>>>>>>>>>>>>>>>>>>>>>> separation
>>>>>>>>>>>>>>>>>>>>>>>>>>>> is
>>>>>>>>>>>>>>>>>>>>>>>>>>>> of particular interest, since the energy minimum
>>>>>>>>>>>>>>>>>>>>>>>>>>>> is so distinct.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>> So based on this the deltaG will correspond to -5.22
>>>>>>>>>>>>>>>>>>>>>>>> as the
>>>>>>>>>>>>>>>>>>>>>>>> initial
>>>>>>>>>>>>>>>>>>>>>>>> state was taken at 0.4 nm corresponding to 0
>>>>>>>>>>>>>>>>>>>>>>>> kcal/mol
>>>>>>>>>>>>>>>>>>>>>>>> as the
>>>>>>>>>>>>>>>>>>>>>>>> moment
>>>>>>>>>>>>>>>>>>>>>>>> corresponding to the minimum is the coordinate from
>>>>>>>>>>>>>>>>>>>>>>>> SMD where last
>>>>>>>>>>>>>>>>>>>>>>>> hydrogen bond was broken. Would you agree?
>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>> Based on the very little information I have, no.  It
>>>>>>>>>>>>>>>>>>>> would appear
>>>>>>>>>>>>>>>>>>>> that
>>>>>>>>>>>>>>>>>>>> the
>>>>>>>>>>>>>>>>>>>> 0.4 nm separation is in fact some metastable state and
>>>>>>>>>>>>>>>>>>>> the true
>>>>>>>>>>>>>>>>>>>> energy
>>>>>>>>>>>>>>>>>>>> minimum is at 0.6 nm of COM separation.  What's going on
>>>>>>>>>>>>>>>>>>>> at that
>>>>>>>>>>>>>>>>>>>> location?
>>>>>>>>
>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>> My mistake. The initial grompp of 1st configuartion (where
>>>>>>>>>>>>>>>> ligand
>>>>>>>>>>>>>>>> stakced on keratin surface) corresponds to 0.6 nm where
>>>>>>>>>>>>>>>> is the minimum. Thus deltaG would be -7.22 kcal/mol. Am I
>>>>>>>>>>>>>>>> right? Or
>>>>>>>>>>>>>>>> Shall I take difference between 0 and 5.22 ?
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>
>>>>>>>>>>
>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>> -7.22 kcal/mol sounds much more logical to me.  If your first
>>>>>>>>>>>> configuration
>>>>>>>>>>>> is at the energy minimum, that's not something you ignore.  The
>>>>>>>>>>>> zero
>>>>>>>>>>>> point
>>>>>>>>>>>> can be set wherever you like with the g_wham flag -zprof0, so
>>>>>>>>>>>> it's
>>>>>>>>>>>> really
>>>>>>>>>>>> rather arbitrary.  The WHAM algorithm simply sets the leftmost
>>>>>>>>>>>> window
>>>>>>>>>>>> (smallest value along the reaction coordinate) to zero to
>>>>>>>>>>>> construct the
>>>>>>>>>>>> remainder of the PMF curve.
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>>>>> I hope you're doing a thorough analysis of
>>>>>>>>>>>>>>>>>>>>>>>>>>>> convergence if you're
>>>>>>>>>>>>>>>>>>>>>>>>>>>> generating
>>>>>>>>>>>>>>>>>>>>>>>>>>>> velocities at the outset of each run, and
>>>>>>>>>>>>>>>>>>>>>>>>>>>> removing
>>>>>>>>>>>>>>>>>>>>>>>>>>>> unequilibrated
>>>>>>>>>>>>>>>>>>>>>>>>>>>> frames
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>>>>> When I use WHAM I skip first 200 ps of each window
>>>>>>>>>>>>>>>>>>>>>>>> as
>>>>>>>>>>>>>>>>>>>>>>>> the
>>>>>>>>>>>>>>>>>>>>>>>> equilibration.
>>>>>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>>> That seems fairly short, especially given the generation
>>>>>>>>>>>>>>>>>>>> of
>>>>>>>>>>>>>>>>>>>> velocities in
>>>>>>>>>>>>>>>>>>>> conjunction with the Parrinello-Rahman barostat, which
>>>>>>>>>>>>>>>>>>>> can be very
>>>>>>>>>>>>>>>>>>>> temperamental.
>>>>>>>>
>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>> Would you suggest e.g. skip 1 ns?
>>>>>>>>>>>>>>>>
>>>>>>>
>>>>>>>>>>
>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>> I'm not going to make an arbitrary guess.  It's up to you to
>>>>>>>>>>>> analyze the
>>>>>>>>>>>> timeframe required for whatever relevant observables to
>>>>>>>>>>>> converge.
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>> -Justin
>>>>>>
>>>>>>
>>>>>>>>
>>>>>>>> Thanks for this.
>>>>>>>>
>>>>>>>> Steven
>>>>>>>>
>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>> --
>>>>>
>>>>>
>>>>>>
>>>>>>
>>>>>> --
>>>>>> gmx-users mailing listgmx-users at gromacs.org
>>>>>> http://lists.gromacs.org/mailman/listinfo/gmx-users
>>>>>> * Only plain text messages are allowed!
>>>>>> * Please search the archive at
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>>>>>> interface or send it togmx-users-request at gromacs.org.
>>>
>>>
>>>
>>> --
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>
>
> --
> ========================================
>
> Justin A. Lemkul, Ph.D.
> Research Scientist
> 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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```