[gmx-users] PMF calculation by umbrella sampling simulations
mpi566 at gmail.com
Thu Apr 30 22:12:34 CEST 2015
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.
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