Re: [AMBER] Cofactor parametrization

From: FyD <>
Date: Thu, 05 Mar 2015 16:43:44 +0100

Dear Francesca,

You must know the total charge (& spin multiplicity) of your molecule
to run a QM job; once you know the total charge value (in relation
with the protonation state (vs pH) of your molecule) you can run the
QM code. That code _might_ give the results you wish if no SCF
convergence or geometry convergence problems are observed.

If you do not provide the right total charge value the QM code will
crash or lead to a totally wrong result.


Concerning geometry of a molecule with multiple formal charges:

- as geometry optimization is (generally) carried out in gas phase the
chemical groups corresponding to these formal charges likely interact
leading to a non-representative optimized geometry; this is a reason
why the building block approach was introduced (see the F-90 R.E.DD.B.

- We do not use sqm at q4md-forcefieldtools - from what I read from
the Amber mailing list this tool seems to have SCF convergence
problems in 'some' cases; and a case could be again molecules with
multiple formal charges. sqm gradient is also loose from what I

R.E.D. Server Dev. interfaces various versions of three QM codes:
Gaussian, GAMESS and Firefly. Each code has its own advantages. If you
are an academic user that means you can create a private account and
use Gaussian.

NADP+ is also in the F-90 R.E.DD.B. project (building block approach):

regards, Francois

> First of all thank you for your kind support,
> I rewrite you because I want to explain what I have to do and why I
> am encountering this problem during the cofactor parametrization.
> I am running MD simulations of one protein 4CV1 pdb code (chain B)
> with cofactor NADPH and also the complex (protein plus cofactor)
> with two different ligands.
> During this first part of my work I was considering for the cofactor
> parametrization 4 negative charges related at the oxygen in the
> phosphate groups, obtained removing 4H after having add hydrogen in
> the original pdb with Sybyl.
> I was using antechamber to obtain my .mol2 and .frcmod files
>> antechamber -i NADPH.pdb -fi pdb -o NADPH.mol2 -fo mol2 --c bcc -s 2 -nc -4
>> parmchk -i NADPH.mol2 -f mol2 -o NADPH.frcmod
> and then processing the files in tleap, creating the library and
> adding the pdb complex to obtain the prmtop and crd files of the
> complex of protein and cofactor. in this case everything is working
> and I was albe to run the minimization and 100ns of MD, both for the
> protein plus cofactor and using the same protocol also for
> protein+cofactor with the two ligands.
> My purpose at this point was simulating the same protein with the
> cofactor considering a different oxidation state of the NADP+, since
> I would like to see the behaviour of my ligands in this two
> different cofactor oxidation state.
> What I was thinking to do was to follow the same protocol just
> modify the atom type in the pyridine ring of the C that are aromatic
> and the N that is aromatic and positive charged in the original pdb.
> At this point I was running antechamber to obtain a mol2 file but
> since I have introduced a positive charge the net charge of the
> molecule would be -3. Unfortunately the command was not able to run
> sqm
>> Error: cannot run "/usr/local/amber12/bin/sqm -O -i -o
>> sqm.out" of bcc() in charge.c properly, exit
> and the error message in the output file was
> QMMM: Unable to achieve self consistency to the tolerances specified
> QMMM: No convergence in SCF after 1000 steps.
> QMMM: E = -0.2208E+07 DeltaE = -0.3539E+03 DeltaP = 0.4770E+00
> QMMM: Smallest DeltaE = -0.2054E+00 DeltaP = 0.3676E+00 Step = 958
> I was trying with different net charge in the antechamber command
> and it was able to run the calculation just when the specified net
> charge of the molecule were - 5 but I don't understand to which
> charges is referring to.
> Then I was trying different strategies and what I saw it's that when
> I don't remove the hydrogen from the phosphate groups and running
> antechamber with a net charge of +1 due to the NADP+ the calculation
> with antechamber command is working.
> So at this point my question are:
> - is this approach correct? anyone had done a similar work?
> - it has sense starting from a pdb structure of a protein
> crystallized with a NADPH (4CV1 pdb code) to obtain a system where
> the cofactor is positive charged NADP+? the introduction of a charge
> in a neutral system will have an impact in the molecular geometry?
> ( and that's why antechamber is not able to calculate the partial
> charges)
> - and how I should consider this hydrogens in the phosphate groups
> for a MD simulations?
> I was looking at the pka of this phosphate groups and a pH 7.4 they
> are dissociated so in the same way that I was considering in the
> first part of the work.
> Furthermore I have to consider that since the cofactor is inside a
> protein it can be affected by the environment, in particular, I can
> expect that just one of the phosphate group is dissociated because
> the close presence of an arginin.
> I would thank all of you for your kind support,
> and for you precious advices
> Francesca
> ________________________________________
> Da: FyD []
> Inviato: marted́ 3 marzo 2015 13.47
> A: AMBER Mailing List
> Oggetto: Re: [AMBER] Cofactor parametrization
> Dear Shahid,
>> Are the ff libraries in these F-90/91 REDDB projects compatible with the
>> new FF ff14SB? Or one has to use the old ff99SB?
> F-90: for the Cornell et al. FF & its successive adaptations -> this
> is written in the abstract
> F-91: for the Duan et al. FF -> this is written in the abstract
> My understanding is that all these Stony-Brook FF FF99SB, FF12SB,
> FF14SB ... FF99SB ;-) are based on the Cornell et al. FF.
> I just checked in the Amber manual 14 page 29:
> 3.1. Specifying which force field you want in LEaP
> File name Original Charge Scheme
> leaprc.ff14SB Cornell et al., 1994
> regards, Francois
>> On Tue, Mar 3, 2015 at 10:18 AM, FyD <> wrote:
>>> Dear Francesca,
>>> You might be interested in the F-90 REDDB project:
>>> NADP+ (and far more) is included...
>>> regards, Francois
>>> > I am running MD of a protein with NADP+ as cofactor.
>>> >
>>> > I have some troubles with the cofactor parametrization:
>>> > antechamber is not recognizing the charge of my mol2 file and as
>>> > well pdb file.
>>> > So I decided to dowload the prep and frcmod files from Amber
>>> > parameter database
>>> > but I don't know how to integrate them with my mol2 or pdb file.

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Received on Thu Mar 05 2015 - 08:00:02 PST
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