Subject: Macromodel_Amber charges: Summary

From: <[email-masked]>
Date: Fri, 11 Nov 1994 14:25:58 +0100 (WET)

Dear all,

I greatly appreciate the replies from Drs. Dave Case, Xinjun Hou and Peter
Shenkin.  My initial posting reads:

> AMBER force field in Macromodel 4.5 gives guanine (also C, T and U) a
> net charge of -0.236.  Does anyone have the same experience with other
> molecules ?

Here is the summary:

AMBER force field has not been designed (at least Amber* in Macromodel 4.5) 
for nucleoside analogues (i.e., molecules with substructures of normal 
natural nucleoside bases).

If one prefer Amber force field for modeling nucleoside analogues, one may 
use his/her own charges or "borrow" the charges from other force fields.  
An alternative is to derive ESP-fitted charges with Gaussian 92 or Mopac 
(I think a new option, QPMEP, will be included in the 95 version).  Since 
the native ESP charges are usually not averaged by either global or 
local symmetry, caution may not be extravagant about the geometrical 
optimization with a large scale of rotations, e.g. conformational analysis.

Below are the responses I received. 

Ciao,

Bingze Wang, Ph.D.

=====================================================================
Date: Tue, 8 Nov 94 17:49:54 PST
From: [email-masked] (David Case)
To: [email-masked]
Subject: Re: CCL:Macromodel_Amber charges

"guanine" by amber nomeclature is only a fragment of a molecule, which
needs to be linked to something else, usually phosphates of a nucleic
acid backbone or something.  I think if you want to make guanosine,
you may need to add h5' and h3' hydrogens, [or something like that].

...dave case

=====================================================================
Date: Wed, 9 Nov 94 09:33:14 -0800
From: [email-masked] (Xinjun Hou)
To: [email-masked]
Subject: Re:  CCL:Macromodel_Amber charges

Hi Bingze:

>AMBER force field in Macromodel 4.5 gives guanine (also C, T and U) a 
>net charge of -0.236.  Does anyone have the same experience with other 
>molecules ?

I have not seen such case yet, unless there is a substructure
definition in your force field which matches your structure partially
and also defines the charges.

I would be intereted to know the answer too!

Xinjun

C     Xinjun J. Hou ([email-masked])                Voice: 619-622-3000
C     Agouron Pharmaceuticals, Inc.                  San Diego, CA 92121

=====================================================================
Date: Wed, 9 Nov 94 10:39:44 -0800
From: [email-masked] (Xinjun Hou)
To: [email-masked]
Subject: Re:  CCL:Macromodel_Amber charges

>I am waiting for your answer. 

Bingze:

   As expected, the total charges I got is -0.236 for
   guanine (2-amino-6-hydorxypurine only)

   I think that this is because macromodel takes guanine as
   part of a ribose monophosphate form. If you make a complete
   structure by going to "INPUT-NUCLEI-GU", you will see why

Xinjun

C     Xinjun J. Hou ([email-masked])                Voice: 619-622-3000
C     Agouron Pharmaceuticals, Inc.                  San Diego, CA 92121
C10110000110100101101110011010100111010101101110010010000110111101110101

=====================================================================

From: "Peter Shenkin" <[email-masked]>
Date: Wed, 9 Nov 1994 12:29:12 -0500
To: <[email-masked]>
Subject: Re: CCL:Macromodel_Amber charges
Cc: [email-masked]

Could you email me a .dat, .com and .log file exhibiting this problem?
I will look into it and let you know what I find.

Technical questions or difficulties about MacroModel are best
addressed to "[email-masked]".

	-P.

-- 
*"Voters prefer the bandwagon to the burning deck" (V. Bonham Carter)*
*Peter S. Shenkin, Box 768 Havemeyer Hall, Chemistry, Columbia Univ.,*
* New York, NY  10027;     [email-masked];     (212) 854-5143  *
** "Illegal immigrants make the best nannies" (Your Congressperson) **

=====================================================================
From: "Peter Shenkin" <[email-masked]>
Date: Thu, 10 Nov 1994 18:06:51 -0500
To: <[email-masked]>
Subject: Re: CCL:Macromodel_Amber charges
Cc: [email-masked], [email-masked]

Mr. Wang,

The charges you obtained were put into the forcefield directly from
Kollman's 1984 paper.  They are designed for use in the context of
ribo- or deoxyribonucleic acids.  When they are used in this context,
the sugar has a net charge of +0.236, which balances the net charge
of -0.236 on the base.  Thus, these substructures must be used in the
proper context in order for the charges to make sense.

I have to say that I am not completely happy with this situation.  I
think that we should not really have charge substructures in our
force-field file that correspond to neutral species, because this can
lead to  funny side-effects, such as you observe, when not used in the
proper context.

Perhaps we should really have, for example, guanine-ribose and
guanine-deoxyribose in the force-field as substructures.  These
overall substructures would be neutral.  Of course, in this situation,
plain old guanine, with no sugar, would not be matched by a special
substructure, and would not be given high-quality parameters unless
someone went out and derived them from QM calculations.

Certainly, as implied by my discussion above, the parameters given
for guanine are appropriate to guanine only with ribose or deoxyribose
attached, and not to isolated guanine.

We will consider altering the force-field to remove things like guanine,
and put them back in attached to the appropriate sugars.  This will
not give you good parameters if what you really want to model is
isolated guanine, but good parameters for isolated guanine do
not, I beleve, exist in standard AMBER.  If they exist in the
literature, or if someone does a credible job of deriving them,
we'd be happy to add them to MacroModel's AMBER* forcefield.

	-P.

-- 
*"Voters prefer the bandwagon to the burning deck" (V. Bonham Carter)*
*Peter S. Shenkin, Box 768 Havemeyer Hall, Chemistry, Columbia Univ.,*
* New York, NY  10027;     [email-masked];     (212) 854-5143  *
** "Illegal immigrants make the best nannies" (Your Congressperson) **

===================  That's all. Thanks for your time ==================