[gmx-users] Replacing a residue and continuing a simulation run
Hello all, I was wondering, is it possible to replace a residue and then continue a simulation using the new parameters/geometry of the new residue? The reason I ask is that I am interested in performing simulations of proteins with tryptophan in its excited state following a lengthy equilibration with TRP in its ground state. I already have reliable excited state atomic charges for the TRP atoms, and I suppose that I will need to change at least some bonded terms to account for the altered geometry of the excited state. I am still in the middle of reading the information that is out there regarding parameterizing new molecules (since I'm using the CHARMM FF, I've been starting to follow Alexander MacKerell's protocols), but I'm still not quite sure as to how one would practically do this residue replacement in the context of a Gromacs run. Will I need to manually edit my .top file, or is there perhaps another way to update the topology file with the new residue following the ground state equilibration? How about coordinates, will I need to transform the TRP coordinates to the excited state geometry by hand? Perhaps the most important question: is there a better way to do the sort of residue replacement I'm contemplating, or is this something that is just inherently going to be a bit messy? Thanks very much for any insight or guidance you can offer! -- -- J. Nathan Scott, Ph.D. Postdoctoral Fellow Department of Chemistry and Biochemistry Montana State University -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/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/Support/Mailing_Lists
Re: [gmx-users] Replacing a residue and continuing a simulation run
J. Nathan Scott wrote: Hello all, I was wondering, is it possible to replace a residue and then continue a simulation using the new parameters/geometry of the new residue? The reason I ask is that I am interested in performing simulations of proteins with tryptophan in its excited state following a lengthy equilibration with TRP in its ground state. I already have reliable excited state atomic charges for the TRP atoms, and I suppose that I will need to change at least some bonded terms to account for the altered geometry of the excited state. I am still in the middle of reading the information that is out there regarding parameterizing new molecules (since I'm using the CHARMM FF, I've been starting to follow Alexander MacKerell's protocols), but I'm still not quite sure as to how one would practically do this residue replacement in the context of a Gromacs run. Will I need to manually edit my .top file, or is there perhaps another way to update the topology file with the new residue following the ground state equilibration? How about coordinates, will I need to transform the TRP coordinates to the excited state geometry by hand? You would have to hack the topology. Coordinates are another matter. If you start making ad hoc changes, then what's the point of a continuation? Presumably, if you've designed the residue's topology correctly (including both bonded and nonbonded parameters), then the residue will adopt the correct geometry on its own. The complication comes with bonded interactions. Are you using constraints? If so, then changing bond lengths will cause the constraints to fail at step 0 (or very soon thereafter) and the simulation will crash. You can get around this by setting continuation = no in the .mdp file, but again I wonder what the value of the continuation is. You'd almost certainly have to forgo the use of .cpt files, supplying instead your .trr and .edr files to preserve as much of the previous ensemble as possible. Even if you're not using constraints, the simulation may still fail if you're suddenly changing bond lengths, angles, etc by anything more than a very small amount. Perhaps the most important question: is there a better way to do the sort of residue replacement I'm contemplating, or is this something that is just inherently going to be a bit messy? I can't see any way around topology hacking. If you need different parameters, you need a different topology. It's going to be a bit messy, and I would encourage you to give some serious thought to the potential pitfalls I listed above. -Justin Thanks very much for any insight or guidance you can offer! -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee 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 listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/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/Support/Mailing_Lists
Re: [gmx-users] Replacing a residue and continuing a simulation run
Hi :) I'd say that if the changes are small you should be able to get away with it. You might want to start off the second part of the run with a smaller time step to relax, though. If the change is from TRP to TRP*, you only need to have a modified topology, without touching the coordinates. You do need to set up a new .tpr file from the the .trr and the modified topology. Hope it helps, Tsjerk On Tue, Mar 15, 2011 at 10:11 PM, Justin A. Lemkul jalem...@vt.edu wrote: J. Nathan Scott wrote: Hello all, I was wondering, is it possible to replace a residue and then continue a simulation using the new parameters/geometry of the new residue? The reason I ask is that I am interested in performing simulations of proteins with tryptophan in its excited state following a lengthy equilibration with TRP in its ground state. I already have reliable excited state atomic charges for the TRP atoms, and I suppose that I will need to change at least some bonded terms to account for the altered geometry of the excited state. I am still in the middle of reading the information that is out there regarding parameterizing new molecules (since I'm using the CHARMM FF, I've been starting to follow Alexander MacKerell's protocols), but I'm still not quite sure as to how one would practically do this residue replacement in the context of a Gromacs run. Will I need to manually edit my .top file, or is there perhaps another way to update the topology file with the new residue following the ground state equilibration? How about coordinates, will I need to transform the TRP coordinates to the excited state geometry by hand? You would have to hack the topology. Coordinates are another matter. If you start making ad hoc changes, then what's the point of a continuation? Presumably, if you've designed the residue's topology correctly (including both bonded and nonbonded parameters), then the residue will adopt the correct geometry on its own. The complication comes with bonded interactions. Are you using constraints? If so, then changing bond lengths will cause the constraints to fail at step 0 (or very soon thereafter) and the simulation will crash. You can get around this by setting continuation = no in the .mdp file, but again I wonder what the value of the continuation is. You'd almost certainly have to forgo the use of .cpt files, supplying instead your .trr and .edr files to preserve as much of the previous ensemble as possible. Even if you're not using constraints, the simulation may still fail if you're suddenly changing bond lengths, angles, etc by anything more than a very small amount. Perhaps the most important question: is there a better way to do the sort of residue replacement I'm contemplating, or is this something that is just inherently going to be a bit messy? I can't see any way around topology hacking. If you need different parameters, you need a different topology. It's going to be a bit messy, and I would encourage you to give some serious thought to the potential pitfalls I listed above. -Justin Thanks very much for any insight or guidance you can offer! -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee 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://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/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/Support/Mailing_Lists -- Tsjerk A. Wassenaar, Ph.D. post-doctoral researcher Molecular Dynamics Group * Groningen Institute for Biomolecular Research and Biotechnology * Zernike Institute for Advanced Materials University of Groningen The Netherlands -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/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/Support/Mailing_Lists
