Subject: difference between Gibbs and MM_PBSA

From: thenmalar rathinavelan <[email-masked]>
Date: Fri, 14 Dec 2001 09:01:48 +0000 (GMT)

Dear gentlepersons,
   I have planned to carry out free energy
calculations using Amber6.0. In relation to this I
like to know what is the difference in calculating the
free energy using Gibbs module and MM-PBSA and which
is more reliable one. Since I am a new user to this I
like to learn the basic regarding these two and please
suggest me proper reference for this.
 
Thank you very much

With Best regards,
Thenmalar

________________________________________________________________________
For Stock Quotes, Finance News, Insurance, Tax Planners, Mutual Funds...
                Visit http://in.finance.yahoo.com/

---

From: David Case <[email-masked]>
Date: Fri, 14 Dec 2001 08:12:21 -0800

> suggest me proper reference for this.

Free energy calculations, such as free energy perturbation or thermodynamic
integration, are potentially very accurate ways of estimating such
differences: with good sampling, they can be as good as the underlying force
fields themselves.

There are lots of good reviews and introductions.  My personal favorites
are:

   Frenkel and Smit, "Understanding Molecular Simulations" (Academic Press).

   Mezei and Beveridge, "Free Energy Simulations", Ann. NY Acad. Sci.
      482:1-23 (1986)

   Kollman, "Free energy calculations: applications to chemical and bio-
      chemical phenomena", Chem. Rev. 93:2395-2417 (1993).

(Of course, the last two are dated, and cover only the basics.)

The MM_PBSA approach takes snapshots from molecular dynamics simulations,
and re-evaluates the energies in a continuum solvent model; solute entropies
are estimated separately.  This model is more easily applicable to large
conformational changes (it does not require creating intermediate states),
but adds errors arrising from the continuum approximation and the entropy
model used those arising from the underlying force field.

My favorite overview of this method is the following:

   Kollman, et. al, Accts. Chem. Res. 33:889-897 (2000).

You should be aware that carefully setting up your system and working hard
to get adequate sampling are key to both methods.  In addition to the 
overviews mentioned above, you should carefully study reports of
applications that are close to the ones you plan to carry out, and should
plan to try to (approximately) reproduce some published results before
starting out on a new system.  Obtaining good estimates of free energy
differences from simulation is a very challenging task.

...hope this helps...please remember that this just represents my thinking,
and that there are in fact many good discussions of the subject available.

...regards...dac

-- 

==================================================================
David A. Case                     |  e-mail:      [email-masked]
Dept. of Molecular Biology, TPC15 |  fax:          +1-858-784-8896
The Scripps Research Institute    |  phone:        +1-858-784-9768
10550 N. Torrey Pines Rd.         |  home page:                   
La Jolla CA 92037  USA            |    http://www.scripps.edu/case
==================================================================