From: bqluan (bqluan_at_uiuc.edu)
Date: Tue Jun 19 2007 - 10:35:02 CDT
I think that it also depends on how you constrain the binding pocket
when you pull the ligand. The work computed in the mentioned way
includes the work to stretch the binding pocket, which converts the part
of the work into potential energy in the deformed binding pocket or
whole host molecule. So, I suggest that you compute the work using
"pulling force times the relative displacement of ligand to binding
pocket surface", which doesn't include the extra elastic potential in
the deformed host molecule. But, I know that it is also tricky to
define the position of binding pocket.
By the way, the stiff spring should be used in the simulation.
On Tue, 2007-06-19 at 00:02 -0500, JC Gumbart wrote:
> I can attempt to answer but someone may correct me:
> 1) I'm pretty sure it would be the former, although it seems at least
> in our group that people calculate it slightly differently (but I am
> pretty sure both ways are equivalent). Please see some papers from
> our group for more specifics on this point (I'm looking at right now
> for instance Jensen et al. "Energetics of glycerol conduction through
> aquaglyceroporin GlpF").
> 2) The PMF is a force profile where as the activation energy is the
> amount of energy required to overcome the initial barrier. I do not
> know if the free energy of activation is different or not. I have
> never calculated a PMF myself, but one way to judge would be the size
> of the activation energy. 100 kJ/mol (~25 kcal/mol) does seem a bit
> large however and would likely only proceed if something else
> provided the energy or a conformational change took place (for
> comparison, thermal energy is only about 0.6 kcal/mol). One point I
> will make is that calculating accurate PMFs requires good sampling,
> so if you only ran one trajectory, it probably accumulated a large
> amount of irreversible work. Additional trajectories, appropriately
> averaged using Jarzynki's equality (again, papers from our group
> would be most helpful), may yield a lower number.
> More experienced people may feel free to chime in here. In any case,
> good luck!
> On Jun 18, 2007, at 11:00 PM, Sting wrote:
> > Hi all:
> > I have performed a series of SMD with a constant velocity of 10 Å/
> > ns to force a ligand release from the binding pocket and try to
> > reconstruct the PMF, and I have some problem as follow:
> > 1. How to compute the works done during the process? Should it be:
> > The displacement of ligand*applied Force or The displacement of the
> > moving point which drag the ligand ?
> > 2. What is the diffrence between the PMF and the Activation Energy
> > as well as that between it and the Free Energy of Activation, and
> > how to verify a reasonable PMF?
> > I really need someone to help me. Thank you in advance!
> > Sting
> > stg1979_at_emails.bjut.edu.cn
> > 2007-06-15
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