Prof Case,
Sorry about my ill-formed statements about the PME treatment and the ion
mutations.
The reason I'm following the approach used by the authors in the article is
that when you do the concurrent dual mutation, you still have to check for
the independence of the two mutations that you are doing.
According to the authors' approach:
Step1: N0 + N0 ---> K+ + Cl-
Step2: K+ + N0 ---> N0 + Cl-
Now they call DG1 for step1 and DG2 for step2. The free energy of mutating
N0 ---> K+ = (DG1 + DG2) / 2 and N0 ---> Cl- = (DG1 - DG2) / 2 (they
provided a theoretical background for this in their methods section).
Further they do a Step3
Individual mutations of N0 ---> K+
and N0 --- Cl-
The results from all these steps were consistent in their work.
So I'm trying to use this approach to my protein-ligand system but at first
I'm trying with KCl in TIP3P water using ff99SB force field in AMBER 11.
That is why I was asking about the restraints during the soft-core
implementation.
Further I noticed that when I set dvdl_norest = 1, the free energy part of
the output file does not print this option.
I have tried to explain this in detail in my previous email. But I can
provide more details if this is not sufficient.
Thanks and regards
Sai
On Thu, Jan 19, 2012 at 2:53 PM, David A Case <case.biomaps.rutgers.edu>wrote:
> On Thu, Jan 19, 2012, Sai Kumar Ramadugu wrote:
>
> > One of the papers that I have come across is title "Accurate Estimates of
> > Free Energy Changes in Charge Mutations", JCTC, 6, 1884.
> >
> > The authors suggest that when charged species are mutated, due to the
> Ewald
> > treatment of electrostatics, there is a self-energy term that appears and
> > one has to account for it and they suggested a method to do dual
> mutations.
>
> The Amber PME scheme (and that in other programs) automatically takes into
> account the self-energy terms, so it is perfectly OK to do TI calculations
> where the total charge changes. Of course, when you finally construct a
> real
> thermodynamic cycle from your results, the total charge will be conserved,
> but
> it is not necessary to make each step conserve charge. This then
> simplifies
> a lot of the TI setup.
>
> ...dac
>
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Wed Jan 25 2012 - 10:30:02 PST
