From: Sting (stg1979_at_emails.bjut.edu.cn)
Date: Tue Jun 19 2007 - 22:38:39 CDT
Thank you bqluan and JC Gumbart, this is really helpful!
>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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