AMBER Archive (2004)

Subject: Re: AMBER: AMBER charges(Cornell et al JACS, 1995) and R.E.D

From: FyD (fyd_at_u-picardie.fr)
Date: Wed May 12 2004 - 11:42:31 CDT

Dear Mikyung,

> I am trying to calculate the charges for neutral Arg.
> In Cornell et al (JACS, 1995) and Cieplak et al (J.Comp.Chem.1995),
> the scheme for fitting the non-terminal amino acides was used with
> blocking groups (ACE, NME).
> The following are my questions according to these two articles.
> 1. Do I need to add two blocking groups to optimize neutral Arg using
> Gaussian(6-31G*)? i.e. ACE-AA-NME in paper

If you want to follow the strategy of Cieplak et al., I guess the answer is
'YES' (after reading the pages 1370-1373)... However, it is ONLY true if your
residue is NOT N-term or C-term, i.e CENTRAL. See below.

> 2. For charge fit, the charges of C=O (C:0.5973, O:-0.5679) or N-H
> (N:-0.4157,
> H: 0.2719) groups in the blocking groups have identical C=O and N-H
> charges
> for adjacent residues in the protein or peptide on pg.1371, Cieplak et
> al (J.Comp.Chem. 1995).

Yes all the residues in the file "all_amino94.in" (CENTRAL AMINO-ACIDS) have the
rules you said (just above). It is cleary explained why in the Cieplak et al
paper: because restraints (with ACE and NME blocking group) were used...

> However, C=O and N-H charges are not all the above charges for all amino
> acids
> in Cornel et al (JACS, 1995). Why do some amino acids have identical N-H
> and
> C=O charges to the ones in blocking groups and some don't?

YES the charges of N, H, C and O are different in the the 'all_aminont94.in' and
'all_aminoct94.in' because the way to get the charges for terminal residues
(N-term and C-term) is different than the one used for CENTRAL amino-acids. Read
pages 1375-1376.

> 3. In R.E.D, can we apply specific charge constranits?
> i.e. accorindg to paper, it seems to put specific C=O and N-H charges
> and do charge fitting for rest atoms.

Directly ? NO

Here is what I do to apply intra-molecular and/or inter-molecular restraints:

- Run R.E.D. controlling (or not) the minimum molecular orientation using one or
several conformations (for multi-conformational RESP fit, I can provide you the
beta version of R.E.D. version 2) without restraints.
=> You get two RESP inputs for the 2 RESP stages: input1 & input2

- In a new directory, modify these inputs manually adding the restraints
(intra-molecular and or inter-molecular) manually (see AMBER manual)

- Re-run RESP without R.E.D. this time using the command provided in the R.E.D.
manual see page: (end of page 12). You can create the two following alias in
your $home/.cshrc:

alias resp1 'resp -O -i input1 -e espot -o output1 -p punch1 -q qout -t qout1 -w
qwts -s esout'
alias resp2 'resp -O -i input2 -e espot -o output2 -p punch2 -q qout1 -t qout2
-w qwts -s esout'

Thus each time you modify your RESP input1&2 to introduce new restraints, you
can execute the 'resp1' and 'resp2' commands... This allows to do a lot of tests
to see if the restraints provided in the input are 'really' taken into account
;-).

> I hope my questions are not complicated.
> If anybody understand how to calculate AMBER charges (Cornell et
> al,JACS, 1995) for amino acids, could you help me out?

I would do:
- Select different conformations for your ARG (see the table page 1362 for which
one you may need)
- Run R.E.D. version II to apply multi-conformation RESP fit (with the X
conformations you selected) controlling the minimum molecular orientation (if
you want to publish the charges: re-producibility)
- Add the restraints you need (i.e. it depends if your ARG is N-term/C-term or
CENTRAL)
- and Re-run RESP after modification of their inputs with the 2 'alias' I
provided you.

Regards, Francois

There are a looooot of informations in the Cieplak et al paper. The difficulty
is to not mix them ;-)

F.-Y. Dupradeau
 --
The Scripps Research Institute, San Diego, CA
Faculte de Pharmacie, UPJV, Amiens, France
 --
http://www.u-picardie.fr/labo/lbpd/fyd.htm
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