[gmx-users] PMF calculation by umbrella sampling simulations

MPI mpi566 at gmail.com
Thu Apr 30 22:12:34 CEST 2015

Hi Justin,

   Thanks for your explanation.
In the tutorial, then what is a good approximate value of free energy
?  if  one follows the protocol.   Is -37 or so kcal mol^-1  ?

Here, 26 windows of COM distances are used, each for 10 ns simulation.

In your original paper,  -50.5 kcal mol^-1 is the free energy for
dissociation of a single peptide from protofibril.
In this full preparation,  you used 31-window setup, each for 10 ns simulation.

I've been aware of the difference between 26 and 31 windows but  questions are

First,  if one obtains a reasonable histogram like


,how can one  tell whether if  the system needs more windows ?
because these overlap windows look appropriate.

Second,   after full preparation, how did you know the free energy of
-50.5 or so  is a  GOOD value ?

Third,  comparing  a coarse ( the tutorial) with a full preparation (
your original paper),  it is somehow unclear that the number of
windows can cause  a significant difference of 13 kcal mol^-1 since
it runs independently for 10 ns in each window.

Please see  PMF curve attached in a simulation of  26 windows, each for 10 ns.


The PMF curve looks reasonable except  when it converges to 37.5 kcal
mol^-1 or so.



Justin Lemkul wrote:
> On 4/30/15 12:43 AM, MPI wrote:
> >   Dear Users,
> >
> >    With GMX 4.6.5, I tried to reproduce a system of the dissociation of
> > a single peptide in an AB42 protofibril with PMF (potential of mean
> > force) calculation in Justin's umbrella sampling tutorial.  He
> > derived the binding energy from PMF from a series of umbrella sampling
> > simulations and obtained a value of  free energy  close to  -50.5
> > kcal mol-1.   But I got a value of -37.5 kcal mol-1 after PMF
> > curve was converged.  The value difference is significant and this
> > raises two questions.  What dose cause this difference of  ~13 kcal mol
> > -1  ?  although I used  GPU for calculations, which is the only
> > modification (cutoff-scheme = Verlet).  What is a reasonable range of
> > binding free energy in this case of AB42 protofibril ?
> >
> As I state in the tutorial and as I have said multiple times on the list (even
> just a few days ago!), you will not produce the PMF profile shown in the
> tutorial unless you follow the exact protocol in the paper (which is linked in
> the tutorial).  The value of -37 or so is what you will achieve if you do what
> the tutorial says, which is a "quick and dirty" approximation of the protocol.
> The full preparation (100 ns of MD on the protofibril, followed by a special
> window setup described in the paper to adequately sample small COM distances)
> will yield the quoted value.
> -Justin

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