Re: [gmx-users] mdp-settings for charmm36 and lipid apl values
Hi, in addition to Chris' comments, I think one good way for getting APL of a lipid mixture is the one proposed by Edholm and Nagle : http://www.cell.com/biophysj/abstract/S0006-3495%2805%2972827-7. The idea is to run simulations at different concentrations of [A] and [B]. Ciao, Patrick Le 09/05/2013 01:06, Christopher Neale a écrit : It is a really bad idea to use standard tip3p with charmm36 lipids (see the Piggot paper that you referenced and also Sapay, N. et al. 2010 J. Comp. Chem. 32, 1400-1410 + probably others). dt 0.001 with nstlist 5 seems like overkill on the nstlist update frequency (not a problem though). Here's how I do charmm36 lipid simulations: constraints = all-bonds lincs-iter = 1 lincs-order = 6 constraint_algorithm = lincs integrator = sd dt = 0.002 tinit = 0 nsteps = 500 nstcomm = 1 nstxout = 500 nstvout = 500 nstfout = 500 nstxtcout = 5 nstenergy = 5 nstlist = 10 nstlog=0 ; reduce log file size ns_type = grid vdwtype = switch rlist = 1.2 rlistlong = 1.3 rvdw = 1.2 rvdw-switch = 0.8 rcoulomb = 1.2 coulombtype = PME ewald-rtol = 1e-5 optimize_fft = yes fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 tc_grps = System tau_t = 1.0 ld_seed = -1 ref_t = 310 gen_temp = 310 gen_vel = yes unconstrained_start = no gen_seed = -1 Pcoupl = berendsen pcoupltype = semiisotropic tau_p = 4 4 compressibility = 4.5e-5 4.5e-5 ref_p = 1.0 1.0 For a pure POPC bilayer with Charmm36 lipids and tips3p water, I get ~ 0.64 nm^2/lipid (not using grid-mat, just looking at box dimensions). If I use regular tip3p instead, the APL decreases a lot and eventually forms a gel. In simple terms of APL and phase, you can get the same results as tips3p (0.64 nm^2/lipid) if you use tip4p (and spce is not too bad, but is still not as close as tip4p). Note tip4p will run faster than tips3p by a large margin. Nevertheless, I use tip3sp in all of my work with charmm36. Also, note that ions can shrink your APL, particularly Na+ (and divalent cations are even worse). My simulations use 50 mM KCl, which basically doesn't affect the average APL (although 50 mM NaCl does noticeably reduce the APL). Finally, I am not convinced that a per-molecule area per lipid is a useful quantity to compare to experimental areas per lipid. I haven't looked at Grid-Mat myself, but there must be a lot of assumptions underlying any analysis that tried to assign an area to a single 3D lipid. If I were you, I'd be looking for expt. results of APL for POPC vs. POPE vs. 70%POPC/30%POPE. Also, are you entirely sure that you didn't mix up the POPC vs. POPE values? It looks to me like a simple labelling error enough that it warrants a second look. Chris. -- original message -- I've been experimenting with simulations of mixed bilayers (512 lipids in total, 70% POPC, 30% POPE) using the charmm36 parameter set in gromacs, and have a couple of questions. I know this has been discussed before, but I'd appreciate some input nonetheless :-) The relevant sections of my mdp-file are pasted below: ; Start time and timestep in ps tinit= 0 dt = 0.001 nsteps = 1 ; NEIGHBORSEARCHING PARAMETERS ; nblist update frequency nstlist = 5 ; ns algorithm (simple or grid) ns_type = grid ; Periodic boundary conditions: xyz, no, xy pbc = xyz periodic_molecules = no ; nblist cut-off rlist= 1.2 ; long-range cut-off for switched potentials rlistlong= 1.4 ; OPTIONS FOR ELECTROSTATICS AND VDW ; Method for doing electrostatics coulombtype = PME rcoulomb-switch = 0 rcoulomb = 1.2 ; Relative dielectric constant for the medium and the reaction field epsilon_r= 1 epsilon_rf = 1 ; Method for doing Van der Waals vdw-type = switch ; cut-off lengths rvdw-switch = 0.8 rvdw = 1.2 ; Apply long range dispersion corrections for Energy and Pressure DispCorr = No ; OPTIONS FOR WEAK COUPLING ALGORITHMS ; Temperature coupling tcoupl = V-rescale nsttcouple = -1 nh-chain-length = 10 ; Groups to couple separately tc-grps = System ; Time constant (ps) and reference temperature (K) tau_t= 0.1 ref_t= 300 ; Pressure coupling pcoupl = Parrinello-Rahman pcoupltype = semiisotropic nstpcouple = -1 This is as far as I can tell from earlier discussions on the list, and also from reading the Piggott et al. paper in JCTC, the correct settings for charmm36. After a simulation of ~50 ns, I use GridMatMD to calculate the area per headgroup of POPC and POPE, respectively, and get what I think are not 100% acceptable results (but maybe they are) For
[gmx-users] mdp-settings for charmm36 and lipid apl values
Hi gmx-users, I've been experimenting with simulations of mixed bilayers (512 lipids in total, 70% POPC, 30% POPE) using the charmm36 parameter set in gromacs, and have a couple of questions. I know this has been discussed before, but I'd appreciate some input nonetheless :-) The relevant sections of my mdp-file are pasted below: ; Start time and timestep in ps tinit= 0 dt = 0.001 nsteps = 1 ; NEIGHBORSEARCHING PARAMETERS ; nblist update frequency nstlist = 5 ; ns algorithm (simple or grid) ns_type = grid ; Periodic boundary conditions: xyz, no, xy pbc = xyz periodic_molecules = no ; nblist cut-off rlist= 1.2 ; long-range cut-off for switched potentials rlistlong= 1.4 ; OPTIONS FOR ELECTROSTATICS AND VDW ; Method for doing electrostatics coulombtype = PME rcoulomb-switch = 0 rcoulomb = 1.2 ; Relative dielectric constant for the medium and the reaction field epsilon_r= 1 epsilon_rf = 1 ; Method for doing Van der Waals vdw-type = switch ; cut-off lengths rvdw-switch = 0.8 rvdw = 1.2 ; Apply long range dispersion corrections for Energy and Pressure DispCorr = No ; OPTIONS FOR WEAK COUPLING ALGORITHMS ; Temperature coupling tcoupl = V-rescale nsttcouple = -1 nh-chain-length = 10 ; Groups to couple separately tc-grps = System ; Time constant (ps) and reference temperature (K) tau_t= 0.1 ref_t= 300 ; Pressure coupling pcoupl = Parrinello-Rahman pcoupltype = semiisotropic nstpcouple = -1 This is as far as I can tell from earlier discussions on the list, and also from reading the Piggott et al. paper in JCTC, the correct settings for charmm36. After a simulation of ~50 ns, I use GridMatMD to calculate the area per headgroup of POPC and POPE, respectively, and get what I think are not 100% acceptable results (but maybe they are) For POPC, I get 59,7 A^2, and for POPE, I get 63,1 A^2. The value for POPE would have been fine I suppose if it hadn't been for the fact that the APL for POPC is smaller. Should it not be larger than POPE? I notice in the Piggott-paper that they in the supplement for some simulations of POPC also get APL's of around 59-60 (without POPE of course), and that the results depend to some extent also on the usage of TIP3P vs TIP3SP water models. I have been using normal TIP3P here. Could anyone comment on (a) my mdp-file settings, and (b) the resulting APL, and tell me if I should be worried about anything? THANKS -- 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] mdp-settings for charmm36 and lipid apl values
On 5/8/13 11:09 AM, Gmx QA wrote: Hi gmx-users, I've been experimenting with simulations of mixed bilayers (512 lipids in total, 70% POPC, 30% POPE) using the charmm36 parameter set in gromacs, and have a couple of questions. I know this has been discussed before, but I'd appreciate some input nonetheless :-) The relevant sections of my mdp-file are pasted below: ; Start time and timestep in ps tinit= 0 dt = 0.001 nsteps = 1 ; NEIGHBORSEARCHING PARAMETERS ; nblist update frequency nstlist = 5 ; ns algorithm (simple or grid) ns_type = grid ; Periodic boundary conditions: xyz, no, xy pbc = xyz periodic_molecules = no ; nblist cut-off rlist= 1.2 ; long-range cut-off for switched potentials rlistlong= 1.4 ; OPTIONS FOR ELECTROSTATICS AND VDW ; Method for doing electrostatics coulombtype = PME rcoulomb-switch = 0 rcoulomb = 1.2 ; Relative dielectric constant for the medium and the reaction field epsilon_r= 1 epsilon_rf = 1 ; Method for doing Van der Waals vdw-type = switch ; cut-off lengths rvdw-switch = 0.8 rvdw = 1.2 ; Apply long range dispersion corrections for Energy and Pressure DispCorr = No ; OPTIONS FOR WEAK COUPLING ALGORITHMS ; Temperature coupling tcoupl = V-rescale nsttcouple = -1 nh-chain-length = 10 ; Groups to couple separately tc-grps = System ; Time constant (ps) and reference temperature (K) tau_t= 0.1 ref_t= 300 ; Pressure coupling pcoupl = Parrinello-Rahman pcoupltype = semiisotropic nstpcouple = -1 This is as far as I can tell from earlier discussions on the list, and also from reading the Piggott et al. paper in JCTC, the correct settings for charmm36. After a simulation of ~50 ns, I use GridMatMD to calculate the area per headgroup of POPC and POPE, respectively, and get what I think are not 100% acceptable results (but maybe they are) For POPC, I get 59,7 A^2, and for POPE, I get 63,1 A^2. The value for POPE would have been fine I suppose if it hadn't been for the fact that the APL for POPC is smaller. Should it not be larger than POPE? I notice in the Piggott-paper that they in the supplement for some simulations of POPC also get APL's of around 59-60 (without POPE of course), and that the results depend to some extent also on the usage of TIP3P vs TIP3SP water models. I have been using normal TIP3P here. Could anyone comment on (a) my mdp-file settings, and (b) the resulting APL, and tell me if I should be worried about anything? The .mdp settings are fine as far as I can tell. If you're concerned about accuracy, you should be analyzing a known system and trying to reproduce it. There is no reason in my mind why a binary lipid system should produce the behavior of a pure lipid system. Lipids affect each other (just like all molecules do). Headgroup interactions and acyl chain packing get more complex with increasing numbers of different lipids. -Justin -- Justin A. Lemkul, Ph.D. Research Scientist 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] mdp-settings for charmm36 and lipid apl values
Thanks Justin, those are good points. A quick follow up, would you (or someone else) consider the APL-values I have for my mixed bilayer system to be good, just ok-ish or plain wrong? THANKS 2013/5/8 Justin Lemkul jalem...@vt.edu On 5/8/13 11:09 AM, Gmx QA wrote: Hi gmx-users, I've been experimenting with simulations of mixed bilayers (512 lipids in total, 70% POPC, 30% POPE) using the charmm36 parameter set in gromacs, and have a couple of questions. I know this has been discussed before, but I'd appreciate some input nonetheless :-) The relevant sections of my mdp-file are pasted below: ; Start time and timestep in ps tinit= 0 dt = 0.001 nsteps = 1 ; NEIGHBORSEARCHING PARAMETERS ; nblist update frequency nstlist = 5 ; ns algorithm (simple or grid) ns_type = grid ; Periodic boundary conditions: xyz, no, xy pbc = xyz periodic_molecules = no ; nblist cut-off rlist= 1.2 ; long-range cut-off for switched potentials rlistlong= 1.4 ; OPTIONS FOR ELECTROSTATICS AND VDW ; Method for doing electrostatics coulombtype = PME rcoulomb-switch = 0 rcoulomb = 1.2 ; Relative dielectric constant for the medium and the reaction field epsilon_r= 1 epsilon_rf = 1 ; Method for doing Van der Waals vdw-type = switch ; cut-off lengths rvdw-switch = 0.8 rvdw = 1.2 ; Apply long range dispersion corrections for Energy and Pressure DispCorr = No ; OPTIONS FOR WEAK COUPLING ALGORITHMS ; Temperature coupling tcoupl = V-rescale nsttcouple = -1 nh-chain-length = 10 ; Groups to couple separately tc-grps = System ; Time constant (ps) and reference temperature (K) tau_t= 0.1 ref_t= 300 ; Pressure coupling pcoupl = Parrinello-Rahman pcoupltype = semiisotropic nstpcouple = -1 This is as far as I can tell from earlier discussions on the list, and also from reading the Piggott et al. paper in JCTC, the correct settings for charmm36. After a simulation of ~50 ns, I use GridMatMD to calculate the area per headgroup of POPC and POPE, respectively, and get what I think are not 100% acceptable results (but maybe they are) For POPC, I get 59,7 A^2, and for POPE, I get 63,1 A^2. The value for POPE would have been fine I suppose if it hadn't been for the fact that the APL for POPC is smaller. Should it not be larger than POPE? I notice in the Piggott-paper that they in the supplement for some simulations of POPC also get APL's of around 59-60 (without POPE of course), and that the results depend to some extent also on the usage of TIP3P vs TIP3SP water models. I have been using normal TIP3P here. Could anyone comment on (a) my mdp-file settings, and (b) the resulting APL, and tell me if I should be worried about anything? The .mdp settings are fine as far as I can tell. If you're concerned about accuracy, you should be analyzing a known system and trying to reproduce it. There is no reason in my mind why a binary lipid system should produce the behavior of a pure lipid system. Lipids affect each other (just like all molecules do). Headgroup interactions and acyl chain packing get more complex with increasing numbers of different lipids. -Justin -- ==**== Justin A. Lemkul, Ph.D. Research Scientist Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justinhttp://www.bevanlab.biochem.vt.edu/Pages/Personal/justin ==**== -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/**mailman/listinfo/gmx-usershttp://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/** Support/Mailing_Lists/Searchhttp://www.gromacs.org/Support/Mailing_Lists/Searchbefore 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_Listshttp://www.gromacs.org/Support/Mailing_Lists -- 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] mdp-settings for charmm36 and lipid apl values
On 5/8/13 12:44 PM, Gmx QA wrote: Thanks Justin, those are good points. A quick follow up, would you (or someone else) consider the APL-values I have for my mixed bilayer system to be good, just ok-ish or plain wrong? I have no basis for making such an assessment, but I know there is literature available for 1:1 POPC/POPE membranes that you should look into. If you want to assess accuracy, you need to be working with a well-described system to reproduce or one that has experimental information available that you are trying to model. -Justin -- Justin A. Lemkul, Ph.D. Research Scientist 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
[gmx-users] mdp-settings for charmm36 and lipid apl values
It is a really bad idea to use standard tip3p with charmm36 lipids (see the Piggot paper that you referenced and also Sapay, N. et al. 2010 J. Comp. Chem. 32, 1400-1410 + probably others). dt 0.001 with nstlist 5 seems like overkill on the nstlist update frequency (not a problem though). Here's how I do charmm36 lipid simulations: constraints = all-bonds lincs-iter = 1 lincs-order = 6 constraint_algorithm = lincs integrator = sd dt = 0.002 tinit = 0 nsteps = 500 nstcomm = 1 nstxout = 500 nstvout = 500 nstfout = 500 nstxtcout = 5 nstenergy = 5 nstlist = 10 nstlog=0 ; reduce log file size ns_type = grid vdwtype = switch rlist = 1.2 rlistlong = 1.3 rvdw = 1.2 rvdw-switch = 0.8 rcoulomb = 1.2 coulombtype = PME ewald-rtol = 1e-5 optimize_fft = yes fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 tc_grps = System tau_t = 1.0 ld_seed = -1 ref_t = 310 gen_temp = 310 gen_vel = yes unconstrained_start = no gen_seed = -1 Pcoupl = berendsen pcoupltype = semiisotropic tau_p = 4 4 compressibility = 4.5e-5 4.5e-5 ref_p = 1.0 1.0 For a pure POPC bilayer with Charmm36 lipids and tips3p water, I get ~ 0.64 nm^2/lipid (not using grid-mat, just looking at box dimensions). If I use regular tip3p instead, the APL decreases a lot and eventually forms a gel. In simple terms of APL and phase, you can get the same results as tips3p (0.64 nm^2/lipid) if you use tip4p (and spce is not too bad, but is still not as close as tip4p). Note tip4p will run faster than tips3p by a large margin. Nevertheless, I use tip3sp in all of my work with charmm36. Also, note that ions can shrink your APL, particularly Na+ (and divalent cations are even worse). My simulations use 50 mM KCl, which basically doesn't affect the average APL (although 50 mM NaCl does noticeably reduce the APL). Finally, I am not convinced that a per-molecule area per lipid is a useful quantity to compare to experimental areas per lipid. I haven't looked at Grid-Mat myself, but there must be a lot of assumptions underlying any analysis that tried to assign an area to a single 3D lipid. If I were you, I'd be looking for expt. results of APL for POPC vs. POPE vs. 70%POPC/30%POPE. Also, are you entirely sure that you didn't mix up the POPC vs. POPE values? It looks to me like a simple labelling error enough that it warrants a second look. Chris. -- original message -- I've been experimenting with simulations of mixed bilayers (512 lipids in total, 70% POPC, 30% POPE) using the charmm36 parameter set in gromacs, and have a couple of questions. I know this has been discussed before, but I'd appreciate some input nonetheless :-) The relevant sections of my mdp-file are pasted below: ; Start time and timestep in ps tinit= 0 dt = 0.001 nsteps = 1 ; NEIGHBORSEARCHING PARAMETERS ; nblist update frequency nstlist = 5 ; ns algorithm (simple or grid) ns_type = grid ; Periodic boundary conditions: xyz, no, xy pbc = xyz periodic_molecules = no ; nblist cut-off rlist= 1.2 ; long-range cut-off for switched potentials rlistlong= 1.4 ; OPTIONS FOR ELECTROSTATICS AND VDW ; Method for doing electrostatics coulombtype = PME rcoulomb-switch = 0 rcoulomb = 1.2 ; Relative dielectric constant for the medium and the reaction field epsilon_r= 1 epsilon_rf = 1 ; Method for doing Van der Waals vdw-type = switch ; cut-off lengths rvdw-switch = 0.8 rvdw = 1.2 ; Apply long range dispersion corrections for Energy and Pressure DispCorr = No ; OPTIONS FOR WEAK COUPLING ALGORITHMS ; Temperature coupling tcoupl = V-rescale nsttcouple = -1 nh-chain-length = 10 ; Groups to couple separately tc-grps = System ; Time constant (ps) and reference temperature (K) tau_t= 0.1 ref_t= 300 ; Pressure coupling pcoupl = Parrinello-Rahman pcoupltype = semiisotropic nstpcouple = -1 This is as far as I can tell from earlier discussions on the list, and also from reading the Piggott et al. paper in JCTC, the correct settings for charmm36. After a simulation of ~50 ns, I use GridMatMD to calculate the area per headgroup of POPC and POPE, respectively, and get what I think are not 100% acceptable results (but maybe they are) For POPC, I get 59,7 A^2, and for POPE, I get 63,1 A^2. The value for POPE would have been fine I suppose if it hadn't been for the fact that the APL for POPC is smaller. Should it not be larger than POPE? I notice in the Piggott-paper that they in the supplement for some simulations of POPC also get APL's of around 59-60 (without POPE of
