Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
Dear Ran, Thanks for answering and sorry to take so long to reply. After your response I went seach for more information about that. What I read here in the list is that some people uses antechamber to generate am1-bcc charges (or RESP charges using Gaussian program) and convert the output files to a .top file (using the amb2gmx.pl script) that can be used in gromacs, however, nobody says the kind of ff they intend to use that charges with. Do these type of charges can also be used with Gromos96 ff ( 43a1)? Thanks in advance! Regards, Josmar Rocha --- Em sex, 27/3/09, Ran Friedman, Biochemisches Inst. r.fried...@bioc.uzh.ch escreveu: De: Ran Friedman, Biochemisches Inst. r.fried...@bioc.uzh.ch Assunto: Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones Para: bije...@yahoo.com.br, Discussion list for GROMACS users gmx-users@gromacs.org Data: Sexta-feira, 27 de Março de 2009, 17:35 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
[gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
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 listgmx-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] loop movement X simulation time
Dear Gromacs users I set a 8 ns MD simulation aiming to get a view insight a hypothesized open and closed state of a protein loop. Many crystallografic structures have been solved but none of then shows the open state. Besides bfactor for the loop region to be high, when analysing a partial result (at 2.5 ns) I could not see any intense conformational change (nor any such open state). I noticed that there are two HB stabilizing the closed state. 1- Was the time I set too short? 2- How much time should set to make possible these interactions to break to allow the open state conformation (I've seen in literature times ranging from 2 to 120 ns to study loop movements). 3- Since the time versus protein backbone RMSD plot shows the equilibration of protein structure after some time is it reasonable to imagine that after that it is not possible such loop movement to be achieved? I apologize If my questions sound naive but that's my first MD simulation. I'd appreciate any help. Josmar Rocha Novos endereços, o Yahoo! que você conhece. Crie um email novo com a sua cara @ymail.com ou @rocketmail.com. http://br.new.mail.yahoo.com/addresses___ gmx-users mailing listgmx-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 [EMAIL PROTECTED] Can't post? Read http://www.gromacs.org/mailing_lists/users.php
