[gmx-users] PMF calculation by umbrella sampling simulations

Justin Lemkul jalemkul at vt.edu
Thu Apr 30 14:45:28 CEST 2015

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 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


More information about the gromacs.org_gmx-users mailing list