[gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
Ran Friedman, Biochemisches Inst.
r.friedman at bioc.uzh.ch
Sun Apr 19 09:38:01 CEST 2009
Dear Josmar,
As for the GROMOS FF, I've included a link to the paper describing the most
recent (AFAIK) version of the FF in one of the recent mailing list massages.
Good luck,
Ran
On Sat, 18 Apr 2009 15:56:11 -0400
"Justin A. Lemkul" <jalemkul at vt.edu> wrote:
>
>
> 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:
>
> http://wiki.gromacs.org/index.php/Parameterization
>
> -Justin
>
>> 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
>>
>>
>>
>>
>> ------------------------------------------------------------------------
>> Veja quais são os assuntos do momento no Yahoo! + Buscados: Top 10
>> <http://br.rd.yahoo.com/mail/taglines/mail/*http://br.maisbuscados.yahoo.com/>
>> - Celebridades
>> <http://br.rd.yahoo.com/mail/taglines/mail/*http://br.maisbuscados.yahoo.com/celebridades/>
>> - Música
>> <http://br.rd.yahoo.com/mail/taglines/mail/*http://br.maisbuscados.yahoo.com/m%C3%BAsica/>
>> - Esportes
>> <http://br.rd.yahoo.com/mail/taglines/mail/*http://br.maisbuscados.yahoo.com/esportes/>
>>
>>
>>
>> ------------------------------------------------------------------------
>>
>> _______________________________________________
>> gmx-users mailing list gmx-users at gromacs.org
>> http://www.gromacs.org/mailman/listinfo/gmx-users
>> Please search the archive at http://www.gromacs.org/search before posting!
>> Please don't post (un)subscribe requests to the list. Use the
>> www interface or send it to gmx-users-request at gromacs.org.
>> Can't post? Read http://www.gromacs.org/mailing_lists/users.php
>
> --
> ========================================
>
> Justin A. Lemkul
> Ph.D. Candidate
> ICTAS Doctoral Scholar
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul[at]vt.edu | (540) 231-9080
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>
> ========================================
> _______________________________________________
> gmx-users mailing list gmx-users at gromacs.org
> http://www.gromacs.org/mailman/listinfo/gmx-users
> Please search the archive at http://www.gromacs.org/search before posting!
> Please don't post (un)subscribe requests to the list. Use the www
>interface or send it to gmx-users-request at gromacs.org.
> Can't post? Read http://www.gromacs.org/mailing_lists/users.php
------------------------------------------------------
Ran Friedman
Postdoctoral Fellow
Computational Structural Biology Group (A. Caflisch)
Institute of Biochemistry
University of Zurich
Winterthurerstrasse 190
CH-8057 Zurich, Switzerland
Tel. +41-44-6355593
Skype: ran.friedman
------------------------------------------------------
More information about the gromacs.org_gmx-users
mailing list