How can you calculate computationally charges for molecules containing
phosphates?
--------------------------------------------------
From: "Ran Friedman, Biochemisches Inst." <r.fried...@bioc.uzh.ch>
Sent: Friday, March 27, 2009 2:35 PM
To: <bije...@yahoo.com.br>; "Discussion list for GROMACS users"
<gmx-users@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...@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@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-requ...@gromacs.org.
Can't post? Read http://www.gromacs.org/mailing_lists/users.php
_______________________________________________
gmx-users mailing list gmx-users@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-requ...@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@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-requ...@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@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-requ...@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.
sp...@xray.bmc.uu.se sp...@gromacs.org http://folding.bmc.uu.se
_______________________________________________
gmx-users mailing list gmx-users@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-requ...@gromacs.org.
Can't post? Read http://www.gromacs.org/mailing_lists/users.php
_______________________________________________
gmx-users mailing list gmx-users@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-requ...@gromacs.org.
Can't post? Read http://www.gromacs.org/mailing_lists/users.php
