AMBER Archive (2008)

Subject: Re: AMBER: Free energy of dissociation

From: David Mobley (dmobley_at_gmail.com)
Date: Thu Jun 05 2008 - 11:22:24 CDT

Fatima,

You also need to be careful about what you mean by "average work". The
Jarzynski equality refers to a specific average -- the exponential
average of the work distribution -- that is equal to the free energy.
Simply taking the arithmetic mean of the work distribution will not
give you the free energy.

Also, if you are trying to compute a "standard" binding free energy,
there are some other nuances to worry about aside from just computing
the dissociation free energy. In particularly, standard binding free
energies are supposed to be reported relative to a specific reference
state, so you need to get this into your calculation somehow. I am not
sure that this issue has been resolved for nonequilibrium free energy
calculations yet (though it is probably possible to figure it out by
analogy to PMF calculations). I think Marty Ytreberg has put some
thought into this though, and you may want to see his related preprint
on arXiv (http://arxiv.org/abs/0710.5132).

Again, a big warning note here (I think I mentioned this in a previous
thread) is that convergence of the exponential average here can be
difficult -- if you haven't already read it, you should really read
Jarzynski's 2002 paper on convergence...

For an example of an umbrella sampling approach you might want to see
Benoit Roux's PMF study from several years ago
(http://www.pnas.org/cgi/content/abstract/102/19/6825).

There are of course recent reviews that touch on various approaches
for free energy calculations with examples. I had one in ARCC recently
(http://www.dillgroup.ucsf.edu/~dmobley/my_papers/arcc_primetime.pdf).

Best wishes,
David

On Thu, Jun 5, 2008 at 5:02 AM, <fatima.chami_at_durham.ac.uk> wrote:
>
> Dear folks,
>
> I am looking to determine the free energy of dissociation of monomer from a
> miscelle. I used the Jarzynski's approach to pull the monomer from the
> miscelle along a reaction coordinate defined as the distance between their
> centre of mass. The same protocol was run for several initial configuration
> taken from a 150 ns MD simulation of miscelle in water.
>
> I wondered if the average work to pull the monomer will certainly represent
> the free energy of dissociation according to the Jarzynski equality.
>
>
> If I have to use the Umbrella sampling approach ... I am not very clear about
> the windows and the overlap ... an example of this would be great
>
> best wishes
> Fatima
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