Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
Dear Josmar, As for the GROMOS FF, I've included a link to the paper describing the most recent (AFAIK) version of the FF in one of the recent mailing list massages. Good luck, Ran On Sat, 18 Apr 2009 15:56:11 -0400 Justin A. Lemkul jalem...@vt.edu wrote: Josmar R. da Rocha wrote: 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! The amb2gmx was created to handle AMBER-to-GROMACS conversion. It is unlikely that it would be useful for ffG43a1. Since 43a1 is a united-atom force field, you have to compensate for the fact that nonpolar hydrogen atoms are absent. Furthermore, quantum charge calculation is not a necessary component of Gromos96 parameter derivation. See, for example: http://wiki.gromacs.org/index.php/Parameterization -Justin 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
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
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
Josmar R. da Rocha wrote: 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! The amb2gmx was created to handle AMBER-to-GROMACS conversion. It is unlikely that it would be useful for ffG43a1. Since 43a1 is a united-atom force field, you have to compensate for the fact that nonpolar hydrogen atoms are absent. Furthermore, quantum charge calculation is not a necessary component of Gromos96 parameter derivation. See, for example: http://wiki.gromacs.org/index.php/Parameterization -Justin 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
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
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 jalem...@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.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
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
Lucio Ricardo Montero Valenzuela wrote: 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? We don't support United atom OPLS because Jorgensen himself does not use it anymore. That if something should indicate for you that the united atom force field has been superseded by the all-atom. Jorgensen himself uses OPLS-AA with TIP4P, so this is probably the best recommendation. Most important, if you chose to use another combination, you basically have to prove that this works as well (whatever that means...) Mensaje citado por Justin A. Lemkul jalem...@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.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
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
Hi, I've recently used OPLS-AA for a similar calculation. It has the advantage that many atom types are already defined in Gromacs and that QM-based calculations give you reasonable charges. Note that it may take considerable simulation time (tens of ns) to discriminate between similar docked poses of the same molecule, though MD can give you a hint. If things were easier docking programs would do a better job. Ran. On Wed, 01 Apr 2009 00:12:31 -0600 Lucio Ricardo Montero Valenzuela lucio...@ibt.unam.mx wrote: 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 jalem...@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.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
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
I wanted the OPLS-UA because my system is large (3 proteins with 2 organic molecules, in water), and, if the G43a1 forcefield gives me a MD speed of 70 ps/day, an all atom model will result much slower. So what else can I do to speed up my MD, to get results in 1-3 months?. Mensaje citado por David van der Spoel sp...@xray.bmc.uu.se: Lucio Ricardo Montero Valenzuela wrote: 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? We don't support United atom OPLS because Jorgensen himself does not use it anymore. That if something should indicate for you that the united atom force field has been superseded by the all-atom. Jorgensen himself uses OPLS-AA with TIP4P, so this is probably the best recommendation. Most important, if you chose to use another combination, you basically have to prove that this works as well (whatever that means...) Mensaje citado por Justin A. Lemkul jalem...@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.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
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
How about MOPAC to calculate the charges for 3-methyladenine (this molecule has a charge +1) for using the G43a1 force field?. -- 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 ___
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
How can you test the ligands when you don't know if they REALLY bind to the protein? -- 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 listgmx-users@gromacs.org
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
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
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
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.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
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
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
[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
Re: [gmx-users] HF/6-31G** ESP derived charges to replace PRODRG assigned ones
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 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
