[gmx-users] about correct methodology to run MD of small molecule in gromacs
Dear Gromacs users, As I have referred before I am simulating small molecules (nucleosides) (around 33 atoms) in vacuum in Gromacs. When I do the simulations at the end I want to select the most stable structure from the trajectory for the next steps. What would be the best methodology to use to run a molecular dynamics for this?: 1) Run an anneling and collect the different frames for the trajectory and then at the end analyze the RSMD, free energy and maybe do clustering for the different frames to select the most stable structure? 2) Do an umbrella anneling similar to the Gromacs tutorial 3"umbrella sampling"?, the only problem here is that I want all dihedral angles to rotate and I do not know how to do this. 3) Do a procedure similar to tutorial 6 "Free energy of solvation" in which I generate the free energy from different lambda values from consecutive simulations. Any suggestions? I am not sure how to proceed correctly here. Kindly, Lazaro -- 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] about correct methodology to run MD of small molecule in gromacs
On 4/18/20 7:39 PM, lazaro monteserin wrote: Dear Gromacs users, As I have referred before I am simulating small molecules (nucleosides) (around 33 atoms) in vacuum in Gromacs. When I do the simulations at the end I want to select the most stable structure from the trajectory for the next steps. What would be the best methodology to use to run a molecular dynamics for this?: 1) Run an anneling and collect the different frames for the trajectory and then at the end analyze the RSMD, free energy and maybe do clustering for the different frames to select the most stable structure? How do you propose to compute the conformational free energy? Note also that no biomolecular force field is validated for use in the gas phase, so the balance of conformational sampling has no guarantee of being physically meaningful. 2) Do an umbrella anneling similar to the Gromacs tutorial 3"umbrella sampling"?, the only problem here is that I want all dihedral angles to rotate and I do not know how to do this. You can enforce dihedral rotation with the pull code, but the tutorial has little use here aside from general concepts. 3) Do a procedure similar to tutorial 6 "Free energy of solvation" in which I generate the free energy from different lambda values from consecutive simulations. The tutorial is for decoupling a solute from water. You have a molecule in vacuum. The only thing to decouple is the molecule itself, which will give you an annihilated, physically nonsensical structure. -Justin -- == Justin A. Lemkul, Ph.D. Assistant Professor Office: 301 Fralin Hall Lab: 303 Engel Hall Virginia Tech Department of Biochemistry 340 West Campus Dr. Blacksburg, VA 24061 jalem...@vt.edu | (540) 231-3129 http://www.thelemkullab.com == -- 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] about correct methodology to run MD of small molecule in gromacs
Dear Dr. Lemkul you are completely right. But then how could I approach this problem to get an answer at the end that make sense? On Sun, Apr 19, 2020 at 4:39 PM Justin Lemkul wrote: > > > On 4/18/20 7:39 PM, lazaro monteserin wrote: > > Dear Gromacs users, > > > > As I have referred before I am simulating small molecules (nucleosides) > > (around 33 atoms) in vacuum in Gromacs. When I do the simulations at the > > end I want to select the most stable structure from the trajectory for > the > > next steps. > > > > What would be the best methodology to use to run a molecular dynamics for > > this?: > > > > 1) Run an anneling and collect the different frames for the trajectory > and > > then at the end analyze the RSMD, free energy and maybe do clustering for > > the different frames to select the most stable structure? > > How do you propose to compute the conformational free energy? Note also > that no biomolecular force field is validated for use in the gas phase, > so the balance of conformational sampling has no guarantee of being > physically meaningful. > > > 2) Do an umbrella anneling similar to the Gromacs tutorial 3"umbrella > > sampling"?, the only problem here is that I want all dihedral angles to > > rotate and I do not know how to do this. > > You can enforce dihedral rotation with the pull code, but the tutorial > has little use here aside from general concepts. > > > 3) Do a procedure similar to tutorial 6 "Free energy of solvation" in > which > > I generate the free energy from different lambda values from consecutive > > simulations. > > The tutorial is for decoupling a solute from water. You have a molecule > in vacuum. The only thing to decouple is the molecule itself, which will > give you an annihilated, physically nonsensical structure. > > -Justin > > -- > == > > Justin A. Lemkul, Ph.D. > Assistant Professor > Office: 301 Fralin Hall > Lab: 303 Engel Hall > > Virginia Tech Department of Biochemistry > 340 West Campus Dr. > Blacksburg, VA 24061 > > jalem...@vt.edu | (540) 231-3129 > http://www.thelemkullab.com > > == > > -- > 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] about correct methodology to run MD of small molecule in gromacs
On 4/19/20 4:12 PM, lazaro monteserin wrote: Dear Dr. Lemkul you are completely right. But then how could I approach this problem to get an answer at the end that make sense? What is the purpose of requiring that the simulation start from the most stable vacuum conformation? There are very few rotatable bonds in a nucleoside and they are likely capable of fairly exhaustive sampling in water, anyway. The force field isn't designed for vacuum so anything you generate is likely to either be irrelevant in water or otherwise easily accessible in water in the first place. -Justin On Sun, Apr 19, 2020 at 4:39 PM Justin Lemkul wrote: On 4/18/20 7:39 PM, lazaro monteserin wrote: Dear Gromacs users, As I have referred before I am simulating small molecules (nucleosides) (around 33 atoms) in vacuum in Gromacs. When I do the simulations at the end I want to select the most stable structure from the trajectory for the next steps. What would be the best methodology to use to run a molecular dynamics for this?: 1) Run an anneling and collect the different frames for the trajectory and then at the end analyze the RSMD, free energy and maybe do clustering for the different frames to select the most stable structure? How do you propose to compute the conformational free energy? Note also that no biomolecular force field is validated for use in the gas phase, so the balance of conformational sampling has no guarantee of being physically meaningful. 2) Do an umbrella anneling similar to the Gromacs tutorial 3"umbrella sampling"?, the only problem here is that I want all dihedral angles to rotate and I do not know how to do this. You can enforce dihedral rotation with the pull code, but the tutorial has little use here aside from general concepts. 3) Do a procedure similar to tutorial 6 "Free energy of solvation" in which I generate the free energy from different lambda values from consecutive simulations. The tutorial is for decoupling a solute from water. You have a molecule in vacuum. The only thing to decouple is the molecule itself, which will give you an annihilated, physically nonsensical structure. -Justin -- == Justin A. Lemkul, Ph.D. Assistant Professor Office: 301 Fralin Hall Lab: 303 Engel Hall Virginia Tech Department of Biochemistry 340 West Campus Dr. Blacksburg, VA 24061 jalem...@vt.edu | (540) 231-3129 http://www.thelemkullab.com == -- 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. Assistant Professor Office: 301 Fralin Hall Lab: 303 Engel Hall Virginia Tech Department of Biochemistry 340 West Campus Dr. Blacksburg, VA 24061 jalem...@vt.edu | (540) 231-3129 http://www.thelemkullab.com == -- 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] about correct methodology to run MD of small molecule in gromacs
I thought this approach initially because I will refine the calculations later at DFT level. What do you think? On Sun, Apr 19, 2020 at 5:17 PM Justin Lemkul wrote: > > > On 4/19/20 4:12 PM, lazaro monteserin wrote: > > Dear Dr. Lemkul you are completely right. But then how could I approach > > this problem to get an answer at the end that make sense? > > What is the purpose of requiring that the simulation start from the most > stable vacuum conformation? There are very few rotatable bonds in a > nucleoside and they are likely capable of fairly exhaustive sampling in > water, anyway. The force field isn't designed for vacuum so anything you > generate is likely to either be irrelevant in water or otherwise easily > accessible in water in the first place. > > -Justin > > > On Sun, Apr 19, 2020 at 4:39 PM Justin Lemkul wrote: > > > >> > >> On 4/18/20 7:39 PM, lazaro monteserin wrote: > >>> Dear Gromacs users, > >>> > >>> As I have referred before I am simulating small molecules (nucleosides) > >>> (around 33 atoms) in vacuum in Gromacs. When I do the simulations at > the > >>> end I want to select the most stable structure from the trajectory for > >> the > >>> next steps. > >>> > >>> What would be the best methodology to use to run a molecular dynamics > for > >>> this?: > >>> > >>> 1) Run an anneling and collect the different frames for the trajectory > >> and > >>> then at the end analyze the RSMD, free energy and maybe do clustering > for > >>> the different frames to select the most stable structure? > >> How do you propose to compute the conformational free energy? Note also > >> that no biomolecular force field is validated for use in the gas phase, > >> so the balance of conformational sampling has no guarantee of being > >> physically meaningful. > >> > >>> 2) Do an umbrella anneling similar to the Gromacs tutorial 3"umbrella > >>> sampling"?, the only problem here is that I want all dihedral angles to > >>> rotate and I do not know how to do this. > >> You can enforce dihedral rotation with the pull code, but the tutorial > >> has little use here aside from general concepts. > >> > >>> 3) Do a procedure similar to tutorial 6 "Free energy of solvation" in > >> which > >>> I generate the free energy from different lambda values from > consecutive > >>> simulations. > >> The tutorial is for decoupling a solute from water. You have a molecule > >> in vacuum. The only thing to decouple is the molecule itself, which will > >> give you an annihilated, physically nonsensical structure. > >> > >> -Justin > >> > >> -- > >> == > >> > >> Justin A. Lemkul, Ph.D. > >> Assistant Professor > >> Office: 301 Fralin Hall > >> Lab: 303 Engel Hall > >> > >> Virginia Tech Department of Biochemistry > >> 340 West Campus Dr. > >> Blacksburg, VA 24061 > >> > >> jalem...@vt.edu | (540) 231-3129 > >> http://www.thelemkullab.com > >> > >> == > >> > >> -- > >> 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. > Assistant Professor > Office: 301 Fralin Hall > Lab: 303 Engel Hall > > Virginia Tech Department of Biochemistry > 340 West Campus Dr. > Blacksburg, VA 24061 > > jalem...@vt.edu | (540) 231-3129 > http://www.thelemkullab.com > > == > > -- > 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] about correct methodology to run MD of small molecule in gromacs
On 4/19/20 4:25 PM, lazaro monteserin wrote: I thought this approach initially because I will refine the calculations later at DFT level. What do you think? If you need a QM reference state for subsequent geometry refinement, just generate the QM-optimized geometry and start your calculations from that. You can then do an energy minimization with the force field to determine how well the molecular mechanics approximation agrees with QM (perhaps not very well as most nucleic acid force fields have not used DFT methods in their derivation). -Justin On Sun, Apr 19, 2020 at 5:17 PM Justin Lemkul wrote: On 4/19/20 4:12 PM, lazaro monteserin wrote: Dear Dr. Lemkul you are completely right. But then how could I approach this problem to get an answer at the end that make sense? What is the purpose of requiring that the simulation start from the most stable vacuum conformation? There are very few rotatable bonds in a nucleoside and they are likely capable of fairly exhaustive sampling in water, anyway. The force field isn't designed for vacuum so anything you generate is likely to either be irrelevant in water or otherwise easily accessible in water in the first place. -Justin On Sun, Apr 19, 2020 at 4:39 PM Justin Lemkul wrote: On 4/18/20 7:39 PM, lazaro monteserin wrote: Dear Gromacs users, As I have referred before I am simulating small molecules (nucleosides) (around 33 atoms) in vacuum in Gromacs. When I do the simulations at the end I want to select the most stable structure from the trajectory for the next steps. What would be the best methodology to use to run a molecular dynamics for this?: 1) Run an anneling and collect the different frames for the trajectory and then at the end analyze the RSMD, free energy and maybe do clustering for the different frames to select the most stable structure? How do you propose to compute the conformational free energy? Note also that no biomolecular force field is validated for use in the gas phase, so the balance of conformational sampling has no guarantee of being physically meaningful. 2) Do an umbrella anneling similar to the Gromacs tutorial 3"umbrella sampling"?, the only problem here is that I want all dihedral angles to rotate and I do not know how to do this. You can enforce dihedral rotation with the pull code, but the tutorial has little use here aside from general concepts. 3) Do a procedure similar to tutorial 6 "Free energy of solvation" in which I generate the free energy from different lambda values from consecutive simulations. The tutorial is for decoupling a solute from water. You have a molecule in vacuum. The only thing to decouple is the molecule itself, which will give you an annihilated, physically nonsensical structure. -Justin -- == Justin A. Lemkul, Ph.D. Assistant Professor Office: 301 Fralin Hall Lab: 303 Engel Hall Virginia Tech Department of Biochemistry 340 West Campus Dr. Blacksburg, VA 24061 jalem...@vt.edu | (540) 231-3129 http://www.thelemkullab.com == -- 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. Assistant Professor Office: 301 Fralin Hall Lab: 303 Engel Hall Virginia Tech Department of Biochemistry 340 West Campus Dr. Blacksburg, VA 24061 jalem...@vt.edu | (540) 231-3129 http://www.thelemkullab.com == -- 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. Assistant Professor Office: 301 Fralin Hall Lab: 303 Engel Hall Virginia Tech Department of Biochemistry 340 West Campus Dr. Blacksburg, VA 24061 jalem...@vt.edu | (540) 231-3129 http://www.thelemkullab.com == -- 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] about correct methodology to run MD of small molecule in gromacs
Thank you very much Dr. Lemkul for the advice On Sun, Apr 19, 2020 at 5:33 PM Justin Lemkul wrote: > > > On 4/19/20 4:25 PM, lazaro monteserin wrote: > > I thought this approach initially because I will refine the calculations > > later at DFT level. What do you think? > > If you need a QM reference state for subsequent geometry refinement, > just generate the QM-optimized geometry and start your calculations from > that. You can then do an energy minimization with the force field to > determine how well the molecular mechanics approximation agrees with QM > (perhaps not very well as most nucleic acid force fields have not used > DFT methods in their derivation). > > -Justin > > > On Sun, Apr 19, 2020 at 5:17 PM Justin Lemkul wrote: > > > >> > >> On 4/19/20 4:12 PM, lazaro monteserin wrote: > >>> Dear Dr. Lemkul you are completely right. But then how could I approach > >>> this problem to get an answer at the end that make sense? > >> What is the purpose of requiring that the simulation start from the most > >> stable vacuum conformation? There are very few rotatable bonds in a > >> nucleoside and they are likely capable of fairly exhaustive sampling in > >> water, anyway. The force field isn't designed for vacuum so anything you > >> generate is likely to either be irrelevant in water or otherwise easily > >> accessible in water in the first place. > >> > >> -Justin > >> > >>> On Sun, Apr 19, 2020 at 4:39 PM Justin Lemkul wrote: > >>> > On 4/18/20 7:39 PM, lazaro monteserin wrote: > > Dear Gromacs users, > > > > As I have referred before I am simulating small molecules > (nucleosides) > > (around 33 atoms) in vacuum in Gromacs. When I do the simulations at > >> the > > end I want to select the most stable structure from the trajectory > for > the > > next steps. > > > > What would be the best methodology to use to run a molecular dynamics > >> for > > this?: > > > > 1) Run an anneling and collect the different frames for the > trajectory > and > > then at the end analyze the RSMD, free energy and maybe do clustering > >> for > > the different frames to select the most stable structure? > How do you propose to compute the conformational free energy? Note > also > that no biomolecular force field is validated for use in the gas > phase, > so the balance of conformational sampling has no guarantee of being > physically meaningful. > > > 2) Do an umbrella anneling similar to the Gromacs tutorial 3"umbrella > > sampling"?, the only problem here is that I want all dihedral angles > to > > rotate and I do not know how to do this. > You can enforce dihedral rotation with the pull code, but the tutorial > has little use here aside from general concepts. > > > 3) Do a procedure similar to tutorial 6 "Free energy of solvation" in > which > > I generate the free energy from different lambda values from > >> consecutive > > simulations. > The tutorial is for decoupling a solute from water. You have a > molecule > in vacuum. The only thing to decouple is the molecule itself, which > will > give you an annihilated, physically nonsensical structure. > > -Justin > > -- > == > > Justin A. Lemkul, Ph.D. > Assistant Professor > Office: 301 Fralin Hall > Lab: 303 Engel Hall > > Virginia Tech Department of Biochemistry > 340 West Campus Dr. > Blacksburg, VA 24061 > > jalem...@vt.edu | (540) 231-3129 > http://www.thelemkullab.com > > == > > -- > 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. > >> Assistant Professor > >> Office: 301 Fralin Hall > >> Lab: 303 Engel Hall > >> > >> Virginia Tech Department of Biochemistry > >> 340 West Campus Dr. > >> Blacksburg, VA 24061 > >> > >> jalem...@vt.edu | (540) 231-3129 > >> http://www.thelemkullab.com > >> > >> == > >> > >> -- > >> 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...@groma
