Hello Thomas and all,
after several very busy days I can finally return to this discussion.
So first of all thanks for your previous reply !
My previous question was in the context of the calculation of absolute
dG_binding using TI whose one part is
dG of decoupling (dG_dec) of the ligand from the receptor binding site
(i.e. necessary work to transport ligand from the
receptor binding site (in the solvent) to vacuum ). Naturally I had on my
mind dG_dec calculation with restraints to prevent
ligand from unwanted movements or even escaping from the binding site for
certain lambda values.
So I was simply wondering if in the case of setting dvdl_norest = 1 (which
prevent from including restraint contribution to dV/dl)
is all what I have to do to filter-out the restraint influence to dG_dec
value. Probably not fully as it is indicated in
this your older contribution
http://archive.ambermd.org/201001/0159.html
where you pointed out that
although dvdl_norest=1 the "analytical correction for the restraints" has
to be done. If I understood well partially also to
include entropic part of dG_dec properly.
I guess that you are speaking here about corrections which are in relevant
Roux articles
e.g.
Biophysical Journal 2006, 91, 2798-2814
J. Phys. Chem. B 2009, 113, 2234–2246
J. Chem. Theory Comput. 2006, 2, 1255-1273
expressed in this form:
a)
k*T*ln(Fr)
b)
k*T*ln(Ft*C0)
Where "k" is Boltzmann constant, T is temperature, Fr and Ft are restraint
correction parameters (Fr for rotational and Ft for translational
restrains ) which might be expressed analytically. These two corrections
has the meaning of the work which is done during the restraint (r,t)
release in case of decoupled ligand (positioned in binding site). If I
understood well they might be interpreted as the entropy gain when
restraints are released.
You probably also spoke about corrections denoted in above Roux articles
as dGsite_r and dGsite_t which has the meaning of the work
necessary to apply relevant restraints in case of fully interacting ligand
(in binding site) and so has to be calculated in
special TI calculation with relevant lambda_r, lambda_t. Again if I am not
wrong this corrections has the meaning of the entropy loss
when r,t restraints are applied.
Please let me know if I understood well your notice about "analytical
correction for the restraints" which is necessary to include
in TI calculation of dG_dec when one using r,t restraints (in case of
dvdl_norest = 1).
Thank you very much in advance for your comments !
Best wishes,
Marek
Dne Fri, 06 Jan 2012 17:06:51 +0100 <steinbrt.rci.rutgers.edu> napsal/-a:
> Hi,
>
>> if I understood well in Amber11 if one would like to calculate dG of
>> decoupling
>> of ligand from receptor using proper restraint it is enough to set
>> parameter dvdl_norest = 1
>> (to prevent including restraint contribution to dV/dl) and that.s all ?
>
> that is enough to give you the dvdl without restraint contribution, which
> I believe is what you want for this type of calculation. You still need
> to
> actually set the restraint, e.g. using the nmropt functionality. The
> restraint code was substantially changed since dvdl_norest was
> implemented
> and I have no recent experience with it, so make sure you test the
> answers
> you get on simple systems first!
>
> Thomas
>
> Dr. Thomas Steinbrecher
> formerly at the
> BioMaps Institute
> Rutgers University
> 610 Taylor Rd.
> Piscataway, NJ 08854
>
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Received on Mon Jan 23 2012 - 16:30:02 PST
