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

Wed Apr 1 08:59:35 CEST 2009

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 atom force field has been superseded by the all-atom.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
> >
> > ----------------------------------------------------------------
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> 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

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