Subject: SUmmary: more AMBER types

From: Charles Letner <[email-masked]>
Date: Mon, 7 Nov 1994 09:06:10 -0800 (PST)

Hello,
	Last week I asked about the validity of using standard atom type
for non-protein molecules.  As promised here is the summary of responses.
Thanks to all who responded,
Chuck

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

The question is, do you believe in mystical properties for amino acids, or are
they just chemicals?  If you believe they're just chemicals, then you can use
the atom types anywhere.  You MAY, in certain cases, have a chemical in which
the particular bond/angle/torsion you're interested in has properties that 
differ significantly from the norm, in which case you need to derive your
own parameters.  Otherwise, a cetain sting of 3 atoms is that string is that
string....  (I wouldn't use the tetrahedral C parameters from AMBER for a
cyclopropyl group, for example.  On the other hand, I've been doing some 
work with carvone, a cyclohexenone, & find no reason not to use standard
parameters for it.  You may find, as I did, that not all your bend parameters
have been defined in AMBER, & have to the H & P method to get THOSE.)
Irene Newhouse

---------------------------
From: Ajay <[email-masked]>

Hi Charles,

	Re: your question about using AMBER atom types for MD on substrates.

i/we have successfully done this on two projects:
	a) Free energy perturbation calculations involving distamycin & DNA
	b) Molecular docking of protein ligand complexes.

Both have worked out successfully.

	In general, of course, this is a difficult question to answer. Also,
i have no idea how new parameters work in conjuction with AMBER. It would
be interesting to see other's experiences.

------------------------------------------
From: George Seibel <[email-masked]>

>        I just finished reading the summary of [email-masked] about
>atom types in AMBER.  It seems that this approach of taking a atom type
>from the AMBER force field and using this as an atom type in a non-protein
>molecule is OK.  However, I'm wondering how general this is.  I'm planning
>on including substrates in some of my upcoming MDs.  As these only contain
>C, H, N, and O,  I can probably find similar atoms among the standard atoms
>of AMBER.  So, is this reasonable or should I still think about creating
>new parameters (ala tha Hopfinger & Pearlstein, 1984 article)?  I'd be
>very interested in opinions as well as aspects that should be considered
>when making this decision.

It's fine for a first approximation.  You should do a few minimizations
of your small molecule and compare the results to experimental structures.
The Cambridge Crystallographic Database is very useful in this regard.
You would also like to get conformational energy differences right, at
least within reason...  These days, you can often obtain the needed energies
>from QM calcs with a healthy basis set.

------------------------------------------
From: Brad Isbister <[email-masked]>

Charles Letner writes about the selection of atom types in AMBER.

The selection of atom types should always use a data set which resembles the
compounds to be investigated.  The original AMBER parameters which were
derived for proteins and nucleic acids are pretty good for the functional
groups found in such systems (peptide backbone, AA sidechains, C, T, G, A, etc).

If your system includes other functional groups, a literature search for AMBER
parameters which better reflect the 'real' system is a good idea.  These new
atom types can be included in an frcmod file for addition to the standard
parameter set.  Several papers have been written on 'non-standard' functional
groups.  In my work, I use the parameters for carbohydrates from S.W Homans,
Biochemistry, 1990, 29, 9110-9118.

If you want to know just what compounds were used to derive the standard AMBER
parameter set, get the original AMBER papers:  Kollman, Case, et al, JACS,
1984, 106, 765-784 and Kollman, Case, et al, J. Comp. Chem., 1986, 7, 230-252.
You should also look in the AMBER manual p23-24 for more info on the parameter
databases.

I've seen rumblings of "Does anyone(else) want to set up a database of
published AMBER parameters (or references to such)?"  But I don't think
anyone has taken the plunge and volunteered.

There is always the possibility that your compound is very different from
anything you can find.  In that case, refer to some papers on deriving atom,
bond, angle, and torsion parameters from spectroscopic data and/or Quantum
Mechanical simulation.  I haven't had to go that route yet.  Perhaps some
others on the CCL can help out with the references?

In the end, Molecular Mechanics is a game of assumptions.  Too many guesses and
your results are worthless or misleading; too few and you'll be running very
long and inefficient simulations.  You'll have to determine how similar the
database compounds are to the compound of interest.

Good Luck!

-Brad