Re: [gmx-users] Umbrella sampling along a dihedral angle
On 12/27/14 1:50 PM, Nash, Anthony wrote: Hi Justin, I think I've shot myself in the foot and I'm trawling the gromacs manual with little success at the moment. I'm trying to define my [ dihedral_restraint ] over my ligand-enzyme complex. The topology of the ligand is in one .itp file and the topology of the enzyme is in a separate .itp file. Therefore, in my top level topology file (system.top) I have: #include ../enzyme.itp #include ../ligand.itp Typically if I want restraints to help equilibrate the system I would just define a posre_NAME.itp with the respective force constants beneath each #include directive. But given that each topology file starts with atom 1 I am a bit unsure how I can define a set of restraints over two topology files. Can this be done? I'm really hoping I won't need to clump all topologies into one big file. Restraints are always numbered with respect to the [moleculetype] to which they apply. As an example: http://www.gromacs.org/Documentation/Errors#Atom_index_n_in_position_restraints_out_of_bounds If your (pseudo)dihedral spans the protein and the ligand, the only way to proceed with a restraint is to have a merged [moleculetype] of protein and ligand. They simply cannot be in separate topologies in this case. -Justin Thanks as ever, Anthony Dr Anthony Nash Department of Chemistry University College London From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se [gromacs.org_gmx-users-boun...@maillist.sys.kth.se] on behalf of Justin Lemkul [jalem...@vt.edu] Sent: 27 December 2014 14:49 To: gmx-us...@gromacs.org Subject: Re: [gmx-users] Umbrella sampling along a dihedral angle On 12/26/14 6:11 PM, Nash, Anthony wrote: Dear Gromacs community, Using enforced rotation potentials I have generated a really smooth rotation of my ligand the catalytic binding domain of my protein. I then put together a simple perl script to calculate the dihedral angle of four particular atoms at each time step using g_angle. Taking a 6 degree interval (for a total of 60 windows to span the 360 degree rotation) I modified the topology with a [ dihedral_restraint ] with the respective dihedral angle for that particular configuation. I plan on then running each window for 10 ns to begin with (according to the PMF profile I can add more time). It is from this point where I am a little stuck. I have gone through a number of posts going back to 2011 with regards to using umbrella sampling along a dihedral angle reaction coordinate. The precise post was from Justin: You'll have to build various configurations that correspond to different dihedral angles (which form the sampling windows), then restrain them. The energy attributed to the restraints is then stored in the .edr file. From these energies, you should be able to construct the energy curve over the sampling windows. There are examples of this in the literature, so I suspect you should be able to find some demonstrations of how it's applied. I was wondering whether gromacs now support this procedure natively? I noticed g_wham has an option -cycl for dihedrals but I am still not sure how this fits in with the traditional gromacs means of generating pull force output as I have only been using distance based rather than angular based umbrella sampling. g_wham is still only really designed to process the output from the pull code, not any generalized restraint. That would be a nice features, but AFAIK it is not in the pipeline. You can de-bias the results like I suggested above, but it's probably more work than it's worth. I would suggest just using Alan Grossfield's WHAM implementation. There, you just need to provide the raw numbers (in this case, the dihedral values) and the force constants used. It will then give you your PMF. We have done this recently; it is very easy. -Justin -- == Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 629 University of Maryland, Baltimore 20 Penn St. Baltimore, MD 21201 jalem...@outerbanks.umaryland.edu | (410) 706-7441 http://mackerell.umaryland.edu/~jalemkul == -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- == Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 629 University of Maryland, Baltimore 20 Penn St. Baltimore, MD 21201 jalem
Re: [gmx-users] Umbrella sampling along a dihedral angle
Hi Justin, Thanks for the reply, always appreciated. I like the way gromacs can handle modular structures by breaking up the topology into separate .itp file. Unfortunately this is the first time I've had to span two subunits with a specific restraint. I quickly knocked together a perl script to combine .itp topology files, and now it's all working fine. Thanks again. Anthony Dr Anthony Nash Department of Chemistry University College London From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se [gromacs.org_gmx-users-boun...@maillist.sys.kth.se] on behalf of Justin Lemkul [jalem...@vt.edu] Sent: 28 December 2014 19:57 To: gmx-us...@gromacs.org Subject: Re: [gmx-users] Umbrella sampling along a dihedral angle On 12/27/14 1:50 PM, Nash, Anthony wrote: Hi Justin, I think I've shot myself in the foot and I'm trawling the gromacs manual with little success at the moment. I'm trying to define my [ dihedral_restraint ] over my ligand-enzyme complex. The topology of the ligand is in one .itp file and the topology of the enzyme is in a separate .itp file. Therefore, in my top level topology file (system.top) I have: #include ../enzyme.itp #include ../ligand.itp Typically if I want restraints to help equilibrate the system I would just define a posre_NAME.itp with the respective force constants beneath each #include directive. But given that each topology file starts with atom 1 I am a bit unsure how I can define a set of restraints over two topology files. Can this be done? I'm really hoping I won't need to clump all topologies into one big file. Restraints are always numbered with respect to the [moleculetype] to which they apply. As an example: http://www.gromacs.org/Documentation/Errors#Atom_index_n_in_position_restraints_out_of_bounds If your (pseudo)dihedral spans the protein and the ligand, the only way to proceed with a restraint is to have a merged [moleculetype] of protein and ligand. They simply cannot be in separate topologies in this case. -Justin Thanks as ever, Anthony Dr Anthony Nash Department of Chemistry University College London From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se [gromacs.org_gmx-users-boun...@maillist.sys.kth.se] on behalf of Justin Lemkul [jalem...@vt.edu] Sent: 27 December 2014 14:49 To: gmx-us...@gromacs.org Subject: Re: [gmx-users] Umbrella sampling along a dihedral angle On 12/26/14 6:11 PM, Nash, Anthony wrote: Dear Gromacs community, Using enforced rotation potentials I have generated a really smooth rotation of my ligand the catalytic binding domain of my protein. I then put together a simple perl script to calculate the dihedral angle of four particular atoms at each time step using g_angle. Taking a 6 degree interval (for a total of 60 windows to span the 360 degree rotation) I modified the topology with a [ dihedral_restraint ] with the respective dihedral angle for that particular configuation. I plan on then running each window for 10 ns to begin with (according to the PMF profile I can add more time). It is from this point where I am a little stuck. I have gone through a number of posts going back to 2011 with regards to using umbrella sampling along a dihedral angle reaction coordinate. The precise post was from Justin: You'll have to build various configurations that correspond to different dihedral angles (which form the sampling windows), then restrain them. The energy attributed to the restraints is then stored in the .edr file. From these energies, you should be able to construct the energy curve over the sampling windows. There are examples of this in the literature, so I suspect you should be able to find some demonstrations of how it's applied. I was wondering whether gromacs now support this procedure natively? I noticed g_wham has an option -cycl for dihedrals but I am still not sure how this fits in with the traditional gromacs means of generating pull force output as I have only been using distance based rather than angular based umbrella sampling. g_wham is still only really designed to process the output from the pull code, not any generalized restraint. That would be a nice features, but AFAIK it is not in the pipeline. You can de-bias the results like I suggested above, but it's probably more work than it's worth. I would suggest just using Alan Grossfield's WHAM implementation. There, you just need to provide the raw numbers (in this case, the dihedral values) and the force constants used. It will then give you your PMF. We have done this recently; it is very easy. -Justin -- == Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 629 University of Maryland, Baltimore 20 Penn St
Re: [gmx-users] Umbrella sampling along a dihedral angle
On 12/26/14 6:11 PM, Nash, Anthony wrote: Dear Gromacs community, Using enforced rotation potentials I have generated a really smooth rotation of my ligand the catalytic binding domain of my protein. I then put together a simple perl script to calculate the dihedral angle of four particular atoms at each time step using g_angle. Taking a 6 degree interval (for a total of 60 windows to span the 360 degree rotation) I modified the topology with a [ dihedral_restraint ] with the respective dihedral angle for that particular configuation. I plan on then running each window for 10 ns to begin with (according to the PMF profile I can add more time). It is from this point where I am a little stuck. I have gone through a number of posts going back to 2011 with regards to using umbrella sampling along a dihedral angle reaction coordinate. The precise post was from Justin: You'll have to build various configurations that correspond to different dihedral angles (which form the sampling windows), then restrain them. The energy attributed to the restraints is then stored in the .edr file. From these energies, you should be able to construct the energy curve over the sampling windows. There are examples of this in the literature, so I suspect you should be able to find some demonstrations of how it's applied. I was wondering whether gromacs now support this procedure natively? I noticed g_wham has an option -cycl for dihedrals but I am still not sure how this fits in with the traditional gromacs means of generating pull force output as I have only been using distance based rather than angular based umbrella sampling. g_wham is still only really designed to process the output from the pull code, not any generalized restraint. That would be a nice features, but AFAIK it is not in the pipeline. You can de-bias the results like I suggested above, but it's probably more work than it's worth. I would suggest just using Alan Grossfield's WHAM implementation. There, you just need to provide the raw numbers (in this case, the dihedral values) and the force constants used. It will then give you your PMF. We have done this recently; it is very easy. -Justin -- == Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 629 University of Maryland, Baltimore 20 Penn St. Baltimore, MD 21201 jalem...@outerbanks.umaryland.edu | (410) 706-7441 http://mackerell.umaryland.edu/~jalemkul == -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Umbrella sampling along a dihedral angle
Thanks for the help Justin. I've found the site: http://membrane.urmc.rochester.edu/content/wham Cheers Anthony Dr Anthony Nash Department of Chemistry University College London From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se [gromacs.org_gmx-users-boun...@maillist.sys.kth.se] on behalf of Justin Lemkul [jalem...@vt.edu] Sent: 27 December 2014 14:49 To: gmx-us...@gromacs.org Subject: Re: [gmx-users] Umbrella sampling along a dihedral angle On 12/26/14 6:11 PM, Nash, Anthony wrote: Dear Gromacs community, Using enforced rotation potentials I have generated a really smooth rotation of my ligand the catalytic binding domain of my protein. I then put together a simple perl script to calculate the dihedral angle of four particular atoms at each time step using g_angle. Taking a 6 degree interval (for a total of 60 windows to span the 360 degree rotation) I modified the topology with a [ dihedral_restraint ] with the respective dihedral angle for that particular configuation. I plan on then running each window for 10 ns to begin with (according to the PMF profile I can add more time). It is from this point where I am a little stuck. I have gone through a number of posts going back to 2011 with regards to using umbrella sampling along a dihedral angle reaction coordinate. The precise post was from Justin: You'll have to build various configurations that correspond to different dihedral angles (which form the sampling windows), then restrain them. The energy attributed to the restraints is then stored in the .edr file. From these energies, you should be able to construct the energy curve over the sampling windows. There are examples of this in the literature, so I suspect you should be able to find some demonstrations of how it's applied. I was wondering whether gromacs now support this procedure natively? I noticed g_wham has an option -cycl for dihedrals but I am still not sure how this fits in with the traditional gromacs means of generating pull force output as I have only been using distance based rather than angular based umbrella sampling. g_wham is still only really designed to process the output from the pull code, not any generalized restraint. That would be a nice features, but AFAIK it is not in the pipeline. You can de-bias the results like I suggested above, but it's probably more work than it's worth. I would suggest just using Alan Grossfield's WHAM implementation. There, you just need to provide the raw numbers (in this case, the dihedral values) and the force constants used. It will then give you your PMF. We have done this recently; it is very easy. -Justin -- == Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 629 University of Maryland, Baltimore 20 Penn St. Baltimore, MD 21201 jalem...@outerbanks.umaryland.edu | (410) 706-7441 http://mackerell.umaryland.edu/~jalemkul == -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Umbrella sampling along a dihedral angle
Hi Justin, I think I've shot myself in the foot and I'm trawling the gromacs manual with little success at the moment. I'm trying to define my [ dihedral_restraint ] over my ligand-enzyme complex. The topology of the ligand is in one .itp file and the topology of the enzyme is in a separate .itp file. Therefore, in my top level topology file (system.top) I have: #include ../enzyme.itp #include ../ligand.itp Typically if I want restraints to help equilibrate the system I would just define a posre_NAME.itp with the respective force constants beneath each #include directive. But given that each topology file starts with atom 1 I am a bit unsure how I can define a set of restraints over two topology files. Can this be done? I'm really hoping I won't need to clump all topologies into one big file. Thanks as ever, Anthony Dr Anthony Nash Department of Chemistry University College London From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se [gromacs.org_gmx-users-boun...@maillist.sys.kth.se] on behalf of Justin Lemkul [jalem...@vt.edu] Sent: 27 December 2014 14:49 To: gmx-us...@gromacs.org Subject: Re: [gmx-users] Umbrella sampling along a dihedral angle On 12/26/14 6:11 PM, Nash, Anthony wrote: Dear Gromacs community, Using enforced rotation potentials I have generated a really smooth rotation of my ligand the catalytic binding domain of my protein. I then put together a simple perl script to calculate the dihedral angle of four particular atoms at each time step using g_angle. Taking a 6 degree interval (for a total of 60 windows to span the 360 degree rotation) I modified the topology with a [ dihedral_restraint ] with the respective dihedral angle for that particular configuation. I plan on then running each window for 10 ns to begin with (according to the PMF profile I can add more time). It is from this point where I am a little stuck. I have gone through a number of posts going back to 2011 with regards to using umbrella sampling along a dihedral angle reaction coordinate. The precise post was from Justin: You'll have to build various configurations that correspond to different dihedral angles (which form the sampling windows), then restrain them. The energy attributed to the restraints is then stored in the .edr file. From these energies, you should be able to construct the energy curve over the sampling windows. There are examples of this in the literature, so I suspect you should be able to find some demonstrations of how it's applied. I was wondering whether gromacs now support this procedure natively? I noticed g_wham has an option -cycl for dihedrals but I am still not sure how this fits in with the traditional gromacs means of generating pull force output as I have only been using distance based rather than angular based umbrella sampling. g_wham is still only really designed to process the output from the pull code, not any generalized restraint. That would be a nice features, but AFAIK it is not in the pipeline. You can de-bias the results like I suggested above, but it's probably more work than it's worth. I would suggest just using Alan Grossfield's WHAM implementation. There, you just need to provide the raw numbers (in this case, the dihedral values) and the force constants used. It will then give you your PMF. We have done this recently; it is very easy. -Justin -- == Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 629 University of Maryland, Baltimore 20 Penn St. Baltimore, MD 21201 jalem...@outerbanks.umaryland.edu | (410) 706-7441 http://mackerell.umaryland.edu/~jalemkul == -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
[gmx-users] Umbrella sampling along a dihedral angle
Dear Gromacs community, Using enforced rotation potentials I have generated a really smooth rotation of my ligand the catalytic binding domain of my protein. I then put together a simple perl script to calculate the dihedral angle of four particular atoms at each time step using g_angle. Taking a 6 degree interval (for a total of 60 windows to span the 360 degree rotation) I modified the topology with a [ dihedral_restraint ] with the respective dihedral angle for that particular configuation. I plan on then running each window for 10 ns to begin with (according to the PMF profile I can add more time). It is from this point where I am a little stuck. I have gone through a number of posts going back to 2011 with regards to using umbrella sampling along a dihedral angle reaction coordinate. The precise post was from Justin: You'll have to build various configurations that correspond to different dihedral angles (which form the sampling windows), then restrain them. The energy attributed to the restraints is then stored in the .edr file. From these energies, you should be able to construct the energy curve over the sampling windows. There are examples of this in the literature, so I suspect you should be able to find some demonstrations of how it's applied. I was wondering whether gromacs now support this procedure natively? I noticed g_wham has an option -cycl for dihedrals but I am still not sure how this fits in with the traditional gromacs means of generating pull force output as I have only been using distance based rather than angular based umbrella sampling. Many thanks to any insight. Anthony -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
