[gmx-users] Umbrella - Force constant

Steven Neumann s.neumann08 at gmail.com
Tue Jul 3 15:16:57 CEST 2012

On Tue, Jul 3, 2012 at 2:04 PM, Justin A. Lemkul <jalemkul at vt.edu> wrote:
> On 7/3/12 8:41 AM, Steven Neumann wrote:
>> Dear Gmx Users,
>> Do you know or can you suggest some results based on the comparison of
>> the force constant in Umbrell Sampling? Any literature?
> That would be lovely, but I've never seen such a thing.  One could probably
> write a book with all the test cases that would be required.  My gut tells
> me that you can't generalize too much in terms of pulling simulations - the
> approach depends on what is being pulled (small molecule, peptide, large
> protein), what the medium is (water, membrane, etc), and what the
> interacting partner is (protein surface, ion channel, binding pocket).
>> As far as I understand when you use the same staring coordinates (from
>> the same pulling simulation) for windows but you just change the force
>> constant (e.g. from 500 to 2000 kJ/mol nm2) you should increase number
>> of windows (for f=2000) as smaller force constant will cover wider
>> neigboruring distances - that makes sense.
>> I am curious whether the final result will be the same? I guess with
>> stronger force it will converge faster but more windows are required.
>> is it the only one difference?
> Without a systematic comparison, it's hard to say, but in theory if one
> samples sufficiently and has good overlap between neighboring windows, the
> results should converge to the same answer.
> If someone knows of some applicable literature that has done such
> comparisons, please post a reference.  I'd love to see it.  Most SMD and US
> methodology is written with hand-waving explanations as to what the authors
> did and why it worked, and I have a suspicion that most reviewers don't have
> a better idea so they can't refute such claims.
> -Justin

Thanks Justin. The only thing I found:

Benoît Roux, The calculation of the potential of mean force using
computer simulations, Computer Physics Communications, Volume 91,
Issues 1–3, 2 September 1995, Pages 275-282, ISSN 0010-4655,

" Furthermore, the convergence properties of umbrella
sampling calculations may be exploited more
effectively using WHAM. Generating short umbrella
sampling simulations for a large number of narrow
windows is computationally more advantageous than
generating longer simulations with a smaller number
of wider windows (...) If Nw simulations are used to cover the
whole range L, the force constant K of the umbrella
sampling potential must be chosen to insure a proper
overlap between the adjacent windows, i.e., each
window should cover a range of dL = L/Nw and the
value of K should be on the order of kBT/dL^2 based
on the magnitude of the rms fluctuations. It follows
that the total simulation time Trot needed to generate
the Nw windows varies as ,~ L2/Nw. Thus, it is more
advantageous to run short umbrella sampling simulations
for a large number of narrow windows (the
simulation time required to prepare and equilibrate
the windows, which is also important, is ignored in
this simple analysis)"

If anyone would find something, please post. that is an interesting
gap in free energy calculations.

> --
> ========================================
> 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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