Re: [AMBER] Cofactor parametrization

From: Hannes Loeffler <>
Date: Thu, 5 Mar 2015 13:34:00 +0000

On Thu, 5 Mar 2015 12:55:06 +0000
Francesca Tessaro <> wrote:

> > 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

See 14.2 towards the end in the manual of Amber14 esp. point 6.

> 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.

_You_ have to know what charge your molecule has as this is an input
parameter to sqm.

> 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

You will have to define what protonation state/tautomer your molecule
most likely has prior to any attempt of deriving charges. And yes,
this is a function of the environment. And yes, charge can have a
tremendous effect on structure and gas phase structures of highly
charged molecules can be wildly different from the state you are
interested in. I have made suggestions how to deal with this before:
e.g. fragment based approach or best to look into the literature as a
cofactor like this has mostly likely been looked into many times before.
Francois' R.E.D. server and associated databases are probably a good
tool and resource for this.


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Received on Thu Mar 05 2015 - 06:00:02 PST
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