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

[Lucio Montero]

How can you calculate computationally charges for molecules containing 
phosphates?


>>>> --------------------------------------------------
>>>> 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
>>>>>
>>>>>
>>>>> _______________________________________________
>>>>> 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
>>>> _______________________________________________
>>>> 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
>>> 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
>>>
>>> ========================================
>>> _______________________________________________
>>> 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
>>>
>>
>>
>> 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.
>> _______________________________________________
>> 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
>
>
> -- 
> 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
> _______________________________________________
> 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