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

Justin A. Lemkul jalemkul at vt.edu
Sat Apr 18 21:56:11 CEST 2009

Josmar R. da Rocha wrote:
> 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!

The amb2gmx was created to handle AMBER-to-GROMACS conversion.  It is unlikely 
that it would be useful for ffG43a1.  Since 43a1 is a united-atom force field, 
you have to compensate for the fact that nonpolar hydrogen atoms are absent. 
Furthermore, quantum charge calculation is not a necessary component of Gromos96 
parameter derivation.  See, for example:



> Regards,
> 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,
>     Ran
>     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
>     problem?
>     > 
>     > 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
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Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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