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

Wed Apr 1 08:12:31 CEST 2009

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?
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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