Subject: RE: Crystal structures

From: David Maxwell <[email-masked]>
Date: Wed, 25 Jan 95 9:12:35 EST

In response to Charles Letner's message:

I am involved with force field parameterization, so I feel competent in
dealing with this issue.  The following question was proposed:

> So the question that comes to mind is: Are the simulation methods that are
> being developed really moving towards reproducing cystal conformations?
> If so, can the current force fields be used to get solution conformations?

I guess it really depends on what you using as the basis for your
parameterization.  If you are primarily using single molecule ab initio
calculations to guide fitting, then your structures will likely match well
with the gas phase structures.  If you parameterize with liquid properties in
mind, then you will, hopefully, match the liquid properties and structure.
If you want to match X-ray ...., etc.  With any force field, it is difficult
to match everything perfectly.  Some do well with matching heats of formation
and other gas phase properties, while others do better in liquids, and
still others are good for NMR or X-ray structures.  Yes, a more advanced force
field could, in principle, solve this problem, but it brings up other
problems, one of which is a decrease in computational efficiency.

You said:

> Many times when reading papers on "optimizing" simulations or
> verifying force fields (I'm speaking to molecular mechanics calculations
> here) the authors compare the simulation results to the crystal structure. 
> In many cases the authors chose the best simulation by the simulation that
> deviates the least from the crystal structure.

I see nothing wrong with comparing to crystal structures, especially if it
is the only structural data you have to make comparisions with.  I would hope
that all force fields would give structures in reasonable agreement to the
X-ray structure.  In the case of proteins, the X-ray structure gives us
important tertiary information that still plays a key role in understanding
how proteins "work their wonders" in a biological setting.  Although their
is no reason why the X-ray structure and the real structure in its natural
setting have to be the same, I think most people would agree that they are
similiar .  As has been stated above and by others; the crystal packing effects
and intermolecular forces between any liquid and the structure would cause 
the major deviation between the natural and X-ray structures.

-Dave Maxwell
Yale University
[email-masked]