Subject: MD/MM combination

From: "Rochus Schmid" <[email-masked]>
Date: Tue, 5 Nov 1996 17:39:33 +0100

Dear Netters:

Please forgive me for this rather simple but long question. I really tried hard
to understand the subject, but it appeared to be more complex than I have
expected (and my knowledge about physical chemistry is too limited). I would be
glad about any explanation or hint.

Question 1:
What kind of "information" do I get, when performing MD simulations with
certain parts of the system kept frozen on its position?

Let's consider the following example:
We have a rather flexible molecule which has functional groups allowing the
formation of hydrogen bonds. Now we put it in a box of water molecules and
calculate the potential energy of the system with a forcefield. If we do an MD
calculation with a fixed geometry of the molecule (just the solvent is moving)
we'll get an ensemble and we can average the potential energy.

Now that's the problem: if I want to compare the energy of two conformations of
the molecule in solution, it doesn't make sense to minimize the whole systems
since there are heaps of local minima of different solvent arrangements. So it
seems a natural choice to take the internal energy of the molecule plus the
average of the solvent energies, right? As a consequence, the energy difference
between the two confromations is now temperature dependent, right?

My conclusion is: at a given temperature (and sufficient sampling) these
energies form a potential energy surface of the molecule which includes
temperature and solvent effects "somehow"? But I don't undestand, what kind of
thermodynamic function this really representates.

Question 2:
If I calculate all internal forces on the atoms of the molecule and average all
forces excerted by the solvent on the molecule, I'll get the gradient on that
potential energy surface mentioned above. (Right?)
That means, I can optimize the structure of the molecule including the
tempearture and solvent effects.

Question 3:
As far as I understood the Thermodynamic Integration method and related
methods, the free energy difference can be calculated by defining a reaction
coordinate  and integrating over the averaged forces along that reaction
coordinate.
I'm not quite clear, where this deviates from the aproach above. If I asume the
reaction coordinate to be the way the optimizer walks from a starting structure
to the minimum, then I always have an averaged force along each step (which
includes however only a sampling over the solvent).
That would imply, that I get something like a free energy "surface". But I'm
somehow not convinced. There must be a "bug" in my thinking, but I couldn't
find it.
It would be very, very helpfull for me if someone could tell me where it is.

Thanx for your patience.
I will summarize if there interest (and it is not too embarassing for me :-).

Best greetings to all of you and especially to Jan Labanowski.

Rochus

-- 

********************************************************************************
Rochus Schmid
Technische Universitaet Muenchen	Tel. 	++49 89 2891 3140
Lehrstuhl f. Anorganische Chemie 1	Fax. 	++49 89 2891 3088
Prof. W. A. Herrmann			E-mail:	
Lichtenbergstrasse 4			[email-masked]
85747 Garching
********************************************************************************

>From [email-masked] Tue Nov  5 13:44 EST 1996
From: Jan Labanowski <[email-masked]>
Date: Tue, 5 Nov 1996 13:44:53 -0500
To: [email-masked]
Subject: FUTURE OF CCL

Just a short note:

I will be out of town until the end of this week... So try to be patient,
I will answer my mail piece by piece when I return. My contact with
the live wire may be unfortunately quite rare for a few days.

Thank you very much for your contributions... Some of you really
sent your checks promptly. It feels realy nice to see that I can count
on you, and we can do a lot together. I will thank you personally when
I am back, and I am sure I will have more to say about how things are
going at the end of the next week.

Thanks again for your patience and trust...

Jan Labanowski
CCL Admin.
[email-masked]