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

Fri Apr 3 09:27:59 CEST 2009

I was thinking that's not such a problem switching tha OPLS-AA, since most
of the atoms in my system are from water, that will remain being spc.

--------------------------------------------------
From: "Lucio Ricardo Montero Valenzuela" <lucioric at ibt.unam.mx>
Sent: Wednesday, April 01, 2009 12:59 AM
To: "Discussion list for GROMACS users" <gmx-users at gromacs.org>
Subject: Re: [gmx-users] HF/6-31G** ESP derived charges to replace
PRODRGassigned ones

> I wanted the OPLS-UA because my system is large (3 proteins with 2 organic
> molecules, in water), and, if the G43a1 forcefield gives me a MD speed of
> 70
> ps/day, an all atom model will result much slower. So what else can I do
> to
> speed up my MD, to get results in 1-3 months?.
> Mensaje citado por David van der Spoel <spoel at xray.bmc.uu.se>:
>
>> Lucio Ricardo Montero Valenzuela wrote:
>> > So it 's better to switch to the OPLS forcefield if I want to compute
>> > the
>> > charges?.
>> > How can I implement the OPLS-UA if my gromacs (version 3.3) only
>> > includes
>> the
>> > OPLS-AA?
>>
>> We don't support United atom OPLS because Jorgensen himself does not use
>> it anymore. That if something should indicate for you that the united
>> atom force field has been superseded by the all-atom. Jorgensen himself
>> uses OPLS-AA with TIP4P, so this is probably the best recommendation.
>> Most important, if you chose to use another combination, you basically
>> have to prove that this "works" as well (whatever that means...)
>>
>> > Mensaje citado por "Justin A. Lemkul" <jalemkul at vt.edu>:
>> >
>> >>
>> >> Lucio Montero wrote:
>> >>> How about MOPAC to calculate the charges for 3-methyladenine (this
>> >>> molecule has a charge +1) for using the G43a1 force field?.
>> >>>
>> >>>
>> >> That may not be a bad place to start, but any parameters applied to a
>> Gromos
>> >> molecule have to reproduce condensed phase thermodynamic observables.
>> >> Empirical
>> >> fitting of the initial parameters may be required.  Refer to the
>> >> primary
>> >> literature.  The reference for the 53a5 and 53a6 parameter sets are
>> published
>> >> in
>> >> JCC, which may provide you with some useful information.
>> >>
>> >> -Justin
>> >>
>> >>> --------------------------------------------------
>> >>> From: "Ran Friedman, Biochemisches Inst." <r.friedman at bioc.uzh.ch>
>> >>> Sent: Friday, March 27, 2009 2:35 PM
>> >>> To: <bije_br at yahoo.com.br>; "Discussion list for GROMACS users"
>> >>> <gmx-users at gromacs.org>
>> >>> Subject: Re: [gmx-users] HF/6-31G** ESP derived charges to replace
>> >>> PRODRGassignedones
>> >>>
>> >>>> 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
>> >> Graduate Research Assistant
>> >> 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
>> >>
>> >> ========================================
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>> >>
>> >
>> >
>> > Lucio Ricardo Montero Valenzuela
>> > Instituto de Biotecnologia, UNAM
>> > Departamento de Biologia Molecular de Plantas
>> > Av. Universidad 2001, Col. Chamilpa
>> > Cuernavaca 62210
>> > Mexico
>> >
>> > ----------------------------------------------------------------
>> > Este mensaje fue enviado desde el servidor Webmail del Instituto de
>> Biotecnologia.
>> > _______________________________________________
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>>
>>
>> --
>> David van der Spoel, Ph.D., Professor of Biology
>> Molec. Biophys. group, Dept. of Cell & Molec. Biol., Uppsala University.
>> Box 596, 75124 Uppsala, Sweden. Phone: +46184714205. Fax: +4618511755.
>> spoel at xray.bmc.uu.se spoel at gromacs.org   http://folding.bmc.uu.se
>> _______________________________________________
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>>
>
>
> Lucio Ricardo Montero Valenzuela
> Instituto de Biotecnologia, UNAM
> Departamento de Biologia Molecular de Plantas
> Av. Universidad 2001, Col. Chamilpa
> Cuernavaca 62210
> Mexico
>
> ----------------------------------------------------------------
> Este mensaje fue enviado desde el servidor Webmail del Instituto de
> Biotecnologia.
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