I would imagine that nucleic acid systems are highly flexible, so there
would be a pretty strong entropic contribution to the binding energy (that
makes it more unfavorable) that is not captured by MM/PBSA. In this case,
binding would require a large, compensating electrostatic/VDW contribution
that is favorable to binding. Also, if the DNA is strained upon binding and
you are only using a single trajectory approach, then this is another source
of bias toward a more favorable binding interaction. A single trajectory
approach will assume that the conformations explored by the free DNA is the
same (strained) space explored by the bound DNA.
To refine your estimate, you may consider trying a multiple trajectory
approach (with MMPBSA.py, you can use a 1-, 2-, or 3-trajectory approach
whereby any trajectory not specified is extracted from the complex
trajectory) with an estimate of the vibrational entropy calculated from
normal mode calculations.
Also, as Kevin pointed out, relative Delta Gs have more meaning from MM/PBSA
calculations than absolute Delta Gs.
Good luck!
Jason
On Wed, Dec 29, 2010 at 9:02 AM, Kevin Hauser <84hauser.gmail.com> wrote:
> Hi, Catherine,
>
>
> I have used MM/PBSA with a similar system and obtained a similarly huge
> binding free energy. However, I was interested in how mutations affected
> the
> binding free energy, the "delta-delta-G". This ddG is what's
> "quantitatively" correct, not, usually, the dG as I believe you have
> reported below.
>
>
> HTH,
> kevin
>
> On Wed, Dec 29, 2010 at 10:26 AM, Catein Catherine
> <askamber23.hotmail.com>wrote:
>
> >
> > Dear Sir/Madam,
> >
> > Any one reported MM/GBSA or MM/PBSA of a binding energy between DNA and
> > Protein could be as large as -400 kcal/mol?
> >
> > Best regards,
> >
> > Catherine.
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
>
>
>
> --
> -- - -
> HK
>
> -------------------------------------------------------
> Kevin Eduard Hauser
> National Science Foundation,
> LSAMP Bridge to the Doctorate Fellow
>
> The Department of Chemistry
> Stony Brook University
> Stony Brook, New York 11794
>
> Phone: (561) 635.1848
> Email: 84hauser.gmail.com
> -------------------------------------------------------
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
Jason M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Graduate Student
352-392-4032
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Received on Wed Dec 29 2010 - 11:00:02 PST
