Subject: Free energy calculation

From: "Rochus Schmid" <[email-masked]>
Date: Tue, 28 Nov 1995 13:51:26 +0100

Dear Netters:

I'm new in that field and I have some questions concerning the calculation of
free energies of sissociation.

I have a molecule like this:

                       A2         B3
                         \       /
                          A1---B1---B2
                         /       \
                        A3        B4

I want to get the free energy of dissociation of bond A1-B1. My potential
energy function is a classical forcefield and the bond A1--B1 is parametrized
via QM-calculations (also the change in the forcefield of the fragments A and B
upon dissociation is parametrized analytically).

David A. Pearlman (J. Chem. Phys. 1993, 98, 8946) suggest thermodynamic
integration to be the method of coice. If I understood it correctly, I have to
sum up the components of the cartesian forces on all atoms along the vector
from A1 to B1 (with oposite signs for the fragments A and B) and integrate the
over the distance between A1 and B1.

My problem are the internal degrees of freedom, which will be "converted" to
rotational and translational degrees of freedom if the coupling parameter
lambda reaches 1 (complete dissociation). I guess, it will take more and more
sampling for increasing lambda. And there must be a point, where it is not
longer reasonable.

What to do then?
Are there any tricks to make life easier?
Any hints?

I would appreciate every comment on this.
Thank you very much in advance.
I will summarize to the net.

Greetings,

Rochus

-- 

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Rochus Schmid
Technische Universitaet Muenchen	Tel. 	++49 89 3209 3140
Anorganisch Chemisches Institut 1	Fax. 	++49 89 3209 3473
Prof. W. A. Herrmann			E-mail:	
Lichtenbergstrasse 4			[email-masked]
85747 Garching
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