I have done the docking with autodock, and I want to do a MD satrting from the docked position. Mensaje citado por "Justin A. Lemkul" <jalem...@vt.edu>:
> > > Lucio Montero wrote: > > How can you test the "ligands" when you don't know if they REALLY bind > > to the protein? > > > > Sounds like a job for docking and/or binding energy calculations. > > -Justin > > > -------------------------------------------------- > > 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
