[gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones

Josmar R. da Rocha bije_br at yahoo.com.br
Sat Apr 18 21:44:21 CEST 2009

Dear Ran,

Thanks for answering and sorry to take so long to reply. After your response I went seach for more information about that. What I read here in the list is that some people uses antechamber to generate am1-bcc charges (or RESP charges using Gaussian program) and convert the output files to a .top file (using the amb2gmx.pl script) that can be used in gromacs, however, nobody says the kind of ff they intend to use that charges with. Do these type of charges can also be used with Gromos96 ff ( 43a1)? Thanks in advance!


Josmar Rocha


--- Em sex, 27/3/09, Ran Friedman, Biochemisches Inst. <r.friedman at bioc.uzh.ch> escreveu:
De: Ran Friedman, Biochemisches Inst. <r.friedman at bioc.uzh.ch>
Assunto: Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
Para: bije_br at yahoo.com.br, "Discussion list for GROMACS users" <gmx-users at gromacs.org>
Data: Sexta-feira, 27 de Março de 2009, 17:35

Dear Josmar,

You haven't written which force field you plan to use. For OPLS and AMBER
QM-based optimisation should be fine. In Gromos, the FF was developed with the
aim of reproducing experimental results and I'm not sure if you can find a
better solution than examining other residues with the same chemical moieties or
use the same approach as reported in the relevant manuscripts. Some software
packages can also be used - these are mostly proprietary and not so easy to use.

Once you derive the parameters, it's a good idea to make some test runs of
the ligands and see if they behave as expected before you actually run a
simulation with the protein. For example, if a conjugate ring system isn't
planar something may be wrong in the setting.

There's no easy solution - this is why it's considered an advanced
topic. It is, however, very important. I've encountered a ligand that leaves
its binding site during a simulation due to wrong parameters (in this case, the
protonation of a protein side chain - FEBS  581, Pages 4120-4124, 2007).

Hope that helped,

On Fri, 27 Mar 2009 12:22:01 -0700 (PDT)
 "Josmar R. da Rocha" <bije_br at yahoo.com.br> wrote:
> Dear users,
> I have been reading some posts about using externally computed charges to
replace Prodrg charges at ligand topology files. Many users commented on the low
trustability given to Prodrg charges (e.g
http://www.mail-archive.com/gmx-users@gromacs.org/msg02360.html ;
http://www.mail-archive.com/gmx-users@gromacs.org/msg17351.html ). Dr. Verli
pointed out the use of semi-empirical methods such as RM1 in cases not involving
simulations with sulphate or phosphate groups (what is not my case) and the use
of QM methods with the 6-31G** basis set, for example, to obtain robust charges
(http://www.mail-archive.com/gmx-users@gromacs.org/msg03410.html). On the other
hand Dr. Mobley defined as a "a bad idea to compute charges for an all-atom
case using QM and then try to convert these to a united atom force field".
Other users advice that the best charges are that compatible with the force
field parametrization
> (http://www.mail-archive.com/gmx-users@gromacs.org/msg10760.html ;
http://www.mail-archive.com/gmx-users@gromacs.org/msg08308.html), usually
pointing to http://wiki.gromacs.org/index.php/Parameterization. Dr Friedman
suggested that "to calculate the electrostatic potential over the whole
molecule, and fit the atomic charges so that they reproduce this potential"
in order to make it less sensitive to small changes in the geometry of the
molecule may give good results
(http://www.mail-archive.com/gmx-users@gromacs.org/msg08308.html). Dr. Lemkul
stressed the need for charges refinement to reproduce experimentally-observed
behavior while trying to use QM charges with Gromos ff. since
"Parameterization under Gromos usually involves empirical derivation of
physical parameters, and free energy calculations using thermodynamic
integration". Few examples of protein-ligand studies using Gromacs and
Gromos96 ff that I have access (from literature) seem to treat it as "take
it for granted" issue (any reference with a more detailed description would
be welcome :-)). Despite reading on this topic I could not compile all the
information in a clear and objective way (may be because I'm in the wrong
track). Let ask you some question that I find would help me to make my ideas
more clear:
> 1-am I overestimating the importance of ligand charges in such a simple
study of protein-small molecule (containg charged Phosphate groups) complex? or
> 1.1-The only way to test for this is doing many different simulation on
the same system using different type of computed charges to see what happen?
> 2-How could I try to choose a method to obtain reasonable charges based on
the reproduction of experimentally-observed behavior if I do not have
experimental data for my system?
> 3-I also would like to know from users dealing with protein-ligand
interactions studies what do you consider a good approach to address this
> Based on what I read I'd have a tendency to use HF/6-31G** ESP derived
charges (with necessary changes as to make it united-atom charges and scaling
that to a integer number for each group). Please, let me know if that strategy
would be as good as a disaster! 
> Thank you very much for the attention.
> Josmar Rocha
>      Veja quais são os assuntos do momento no Yahoo! +Buscados
> http://br.maisbuscados.yahoo.com

      Veja quais são os assuntos do momento no Yahoo! +Buscados
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