Subject: Protein Force fields

From: Charles Letner <[email-masked]>
Date: Wed, 8 Dec 1993 13:06:32 -0800 (PST)

Hello all,
	Last week I posted a question concerning the kollman all-atom vs
the kollman united-atom force field.  I later sent a couple of references
to the board.  One of these by Kini and Evans.  I just found another paper
by them from 1992 that I thought some of you might be interested in.  It
compares the all-atom and united-atom versions of the kollman force field. 
That reference is:
	Kini, R. M., and Eveans, J. E., Comparison of Protein Models
Minimized by the All-Atom and United-Atom Models in the AMBER Force Field:
Correlation of RMS deviation with Crystallographic R Factor and Size, J.
Biomol. Str. & Dyn., 10, 2 (1992) pg. 265-279.
	Having said that, I've also just finished the series of two papers
by Roterman, Lambert, Gibson, and Scheraga (1989) from J. Biomol. Stru. &
Dyn.  These papers have me kind of stumped.  These papers compare CHARMM,
AMBER, and ECEPP for modeling proteins.  If I read them right they come
down pretty hard on these force fields.  In fact the last line of the
second paper says that conformational studies by these force fields may
give results that are "entirely misleading".  Further, they state that the
AMBER force field may be inappropriate for dynamics simulations.  I'm
getting ready to start some dynamics simulations using AMBER.  Obviously
I'm somewhat concerned now.  I would sincerely appreciate any comments
some of you might have on this paper.  Also any comments or references
that would help understand the validity of M/M and dynamics would be
welcome.
Thanks and I am looking forward to your comments.
Chuck

Charles Letner
Wright State University
Department of Biochemistry
Dayton, OH 45435
e-mail: [email-masked]

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From: [email-masked] (David Case)
Date: Wed, 8 Dec 93 12:26:03 PST

Charles Letner wrote:
> some of you might have on this paper.  

Peter Kollman and Ken Dill wrote a reponse to this paper: "Decisions in
Force Field Development: An Alternative to those Described by Roterman
et al."  J. Biomol. Struct. Dyn.  8:1103-1107 (1991) which is worth
looking at.

Charlie Brooks and I also considered some of the arguments in the
Roterman et al papers in our recent article in Chemical Reviews, 93:
2487-2502 (1993).

My view is that the phrase "entirely misleading" is a little harsh, but
it clearly depends on what aspects of the calculations you are looking
at.  Roterman et al do make a good point that some pretty fundamental
features of protein conformations are different with different force
fields, and one needs to be very careful in interpreting simulation
results.  There are often features of dynamics simulations that are
quite insensitive to the details of the force field; you might want to
consider a paper that Martha Teeter and I wrote for some examples: J.
Phys. Chem. 94: 8091-8097 (1990).

You might also want to consider some of the work of Julian Tirado-Rives
and Bill Jorgensen, e.g. JACS 112:2773-2781 (1990) and references
therein to earlier work.

This list just scratches the surface, but it may help you to get
started.

Hope this helps....dave case