[gmx-users] WHAM with Pull coordinate angle-axis
Dear GROMACS users, I used the new Pull Geometry angle-axis to define the angle between a peptide (with two c-alpha atoms) and the z-axis as pull coordinate. I have generated a pull trajectory where this angle changes over time from about 80 degree to 0 degree approximately, over the total time of about 1 ns. I now want to perform Umbrella Sampling along this reaction coordinate and extracted windows with a spacing of ca 4 degree, and I have simulated each window for about 2 ns. When I use gmx wham -ix pullx-files.dat -it tpr-files.dat I get somehow reasonable histograms: https://www.dropbox.com/s/9mz0gnufdxo1j6r/histo.png?dl=0 but the profile.xvg file only has NaN in the y column. No further error messages occur. Also, if I use -if pullf-files at input, the histograms are plainly wrong, each just spans about half a degree. Do you know whether the wham implementation of GROMACS can be used with the new pull geometries to generate a PMF? Has someone tested this out yet? Also, which alternative would you suggest for such angle-based PMF? Would PLUMED be an option? Thank you very much in advance Lukas -- 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] Flat-bottomed potential for Sampling in particular volume
Dear GROMACS user, I use the pull code to pull one peptide away from a larger globular protein. For subsequent Umbrella Sampling analyses, I want to keep the peptide within a certain (cylindric, say) volume. However, I want to define the longitudinal axis of the cylider running parallel to the pull direction and the cylinder centered in the box. The peptide's exact pull path would run approximately near the surface of the cylinder. Is there a way to realize this scenario with the position_restraints directive using flat_bottomed function type? As far as I understand the position_restraint directive, the volume is always centered at the particular atom, which will be restrained. That does not really correspond to my case. Perhaps I'm wrong here. Another way to put it would be having a force acting on the peptide pulling it orthogonal to the original pull direction back to the center longitudinal of the box in an harmonic fashion. I basically want to restrain the volume in the which the peptide is sampled, but the peptide, in its initial conformation is not supposed to be the center of this volume. Thank you very much in advance. Regards -- 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] PMF steadily increasing
Thank you again for your remarks. This is what I found so far: (1) With gmx mindist it was very clear that protein and peptide do not interact. For the last 5 or 6 Umbrella Windows, the minimal distance between the Pull groups was at least 2 nm (2) That is indeed the case. The protein has net charge -1 and the peptide has charge +3. Can you tell me what effect this might have? I am unaware that this might cause problems. (3) I tried this, but this showed no apparent effect on the shape of the curve. (4) I do not understand in how far WHAM cares about the COM-COM distances. I extract my frames from pull.xtc and I do not see each COM-COM distance that would be required to have exactly, say, 0.1 nm spacing, so I use a script which selects frames which resemble 0.1 nm spacing as closely as possible, so there might some deviation. 2016-06-16 21:24 GMT+02:00 Lukas Zimmermann <luk.zi...@gmail.com>: > Thank you very much for your suggestions. I will check your individual > remarks and provide feedback. > > 2016-06-15 19:01 GMT+02:00 Christopher Neale <chris.ne...@alum.utoronto.ca > >: > >> (1) Are the protein and peptide really never interacting at d=7 nm? I >> presume you've got a peptide that would be maybe 5 nm long when fully >> extended, and your dG minimum is at 1.5 nm, so giving half the peptide >> length that would imply possible contact at 4 nm, so I expect 7 nm is >> sufficient, but gmx mindist can tell you for certain. For example, if the >> protein forms an overhanging pocket around the binding site, then it is >> quite possible that an unfolded peptide would be sometimes (even rarely) >> contacting a 568 residue protein even at a COM-COM distance of 7 nm. >> >> (2) net charge positive on one and negative on the other? >> >> (3) unconverged? Did you try eliminating the first half of your >> production sampling and see if this fixes the issue? >> >> (4) did you do wham properly? Your mdp file indicate that your windows >> are not *exactly* at 0.1 and 0.2 nm increments (use of >> pull_coord1_start=yes), which is fine but only as long as wham doesn't >> think your windows are exactly at these increments. >> >> There may be some entropy change as the peptide becomes unbound and can >> then sample full X and Y, but on its own that should not continue to impact >> the sampling after contact is permanently broken. >> ____ >> From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se < >> gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Lukas >> Zimmermann <luk.zi...@gmail.com> >> Sent: 15 June 2016 12:45:51 >> To: gmx-us...@gromacs.org >> Subject: [gmx-users] PMF steadily increasing >> >> Dear GROMACS community, >> >> I performed umbrella sampling study to estimate the binding free energy >> between a globular >> protein with 568 residues and a small peptide with 13 residues. I use the >> pull code with k = 800 and rate = 0.005 to generate the initial >> conformations over the time course of 1200 ps. The >> center of masses distance between the pull groups ranges from 1.4 nm ad >> 7.8 nm in the pull trajectory. >> >> I then extract conformations from pull.xtc with a spacing of 0.1 nm until >> 3 >> nm distance >> and a spacing of 0.2 nm for the remainder, yielding 38 windows in total. >> After having >> equilibrated each window with NVT and NPT under full position restraints, >> I >> conducted >> production simulation under NPT ensemble for 14 ns for each window. >> Finally, gmx wham >> computed the PMF curve which you can see here: >> >> https://www.dropbox.com/s/fp7ol41qoyokmjm/profile.xvg?dl=0 >> >> and this is the associated histogram: >> >> https://www.dropbox.com/s/bp6obymjc2qeu37/histo.xvg?dl=0 >> >> Please find here my MDP pull parameters: >> >> pull= yes >> pull_ngroups= 2 >> pull_ncoords= 1 >> pull_group1_name= chainB; Protein >> pull_group2_name= chainC; Peptide >> pull_coord1_type= umbrella >> pull_coord1_geometry= distance >> pull_coord1_groups = 1 2 >> pull_coord1_dim = N N Y >> pull_coord1_rate= 0.0 >> pull_coord1_k = 800 >> pull_coord1_start = yes >> >> >> I would now be very interested why the curve does not become flat beyond >> some certain distance, but rather seems to increase in a linear fashion, >> though the distance between the pull groups is sufficiently large. Could >> this be related to entropic effects? Is th
Re: [gmx-users] PMF steadily increasing
Thank you very much for your suggestions. I will check your individual remarks and provide feedback. 2016-06-15 19:01 GMT+02:00 Christopher Neale <chris.ne...@alum.utoronto.ca>: > (1) Are the protein and peptide really never interacting at d=7 nm? I > presume you've got a peptide that would be maybe 5 nm long when fully > extended, and your dG minimum is at 1.5 nm, so giving half the peptide > length that would imply possible contact at 4 nm, so I expect 7 nm is > sufficient, but gmx mindist can tell you for certain. For example, if the > protein forms an overhanging pocket around the binding site, then it is > quite possible that an unfolded peptide would be sometimes (even rarely) > contacting a 568 residue protein even at a COM-COM distance of 7 nm. > > (2) net charge positive on one and negative on the other? > > (3) unconverged? Did you try eliminating the first half of your production > sampling and see if this fixes the issue? > > (4) did you do wham properly? Your mdp file indicate that your windows are > not *exactly* at 0.1 and 0.2 nm increments (use of pull_coord1_start=yes), > which is fine but only as long as wham doesn't think your windows are > exactly at these increments. > > There may be some entropy change as the peptide becomes unbound and can > then sample full X and Y, but on its own that should not continue to impact > the sampling after contact is permanently broken. > > From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se < > gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Lukas > Zimmermann <luk.zi...@gmail.com> > Sent: 15 June 2016 12:45:51 > To: gmx-us...@gromacs.org > Subject: [gmx-users] PMF steadily increasing > > Dear GROMACS community, > > I performed umbrella sampling study to estimate the binding free energy > between a globular > protein with 568 residues and a small peptide with 13 residues. I use the > pull code with k = 800 and rate = 0.005 to generate the initial > conformations over the time course of 1200 ps. The > center of masses distance between the pull groups ranges from 1.4 nm ad > 7.8 nm in the pull trajectory. > > I then extract conformations from pull.xtc with a spacing of 0.1 nm until 3 > nm distance > and a spacing of 0.2 nm for the remainder, yielding 38 windows in total. > After having > equilibrated each window with NVT and NPT under full position restraints, I > conducted > production simulation under NPT ensemble for 14 ns for each window. > Finally, gmx wham > computed the PMF curve which you can see here: > > https://www.dropbox.com/s/fp7ol41qoyokmjm/profile.xvg?dl=0 > > and this is the associated histogram: > > https://www.dropbox.com/s/bp6obymjc2qeu37/histo.xvg?dl=0 > > Please find here my MDP pull parameters: > > pull= yes > pull_ngroups= 2 > pull_ncoords= 1 > pull_group1_name= chainB; Protein > pull_group2_name= chainC; Peptide > pull_coord1_type= umbrella > pull_coord1_geometry= distance > pull_coord1_groups = 1 2 > pull_coord1_dim = N N Y > pull_coord1_rate= 0.0 > pull_coord1_k = 800 > pull_coord1_start = yes > > > I would now be very interested why the curve does not become flat beyond > some certain distance, but rather seems to increase in a linear fashion, > though the distance between the pull groups is sufficiently large. Could > this be related to entropic effects? Is there a way to > have the PMF properly normalized? > > The force field here is GROMOS 53a6 with SPC water. Temperature is coupled > to > 310 K and pressure to 1 bar. Cutoffs are 1.4 nm, longe range ES are > resolved with PME > and DispCorr is set to EnerPress. Bonds are constrained with LINCS. > > The Protein is prevented from rotation by having three CA atoms restrained > with FC 1000. > > > Thank you very much, I appreciate any help and suggestions. > > Lukas > -- > 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/
[gmx-users] PMF steadily increasing
Dear GROMACS community, I performed umbrella sampling study to estimate the binding free energy between a globular protein with 568 residues and a small peptide with 13 residues. I use the pull code with k = 800 and rate = 0.005 to generate the initial conformations over the time course of 1200 ps. The center of masses distance between the pull groups ranges from 1.4 nm ad 7.8 nm in the pull trajectory. I then extract conformations from pull.xtc with a spacing of 0.1 nm until 3 nm distance and a spacing of 0.2 nm for the remainder, yielding 38 windows in total. After having equilibrated each window with NVT and NPT under full position restraints, I conducted production simulation under NPT ensemble for 14 ns for each window. Finally, gmx wham computed the PMF curve which you can see here: https://www.dropbox.com/s/fp7ol41qoyokmjm/profile.xvg?dl=0 and this is the associated histogram: https://www.dropbox.com/s/bp6obymjc2qeu37/histo.xvg?dl=0 Please find here my MDP pull parameters: pull= yes pull_ngroups= 2 pull_ncoords= 1 pull_group1_name= chainB; Protein pull_group2_name= chainC; Peptide pull_coord1_type= umbrella pull_coord1_geometry= distance pull_coord1_groups = 1 2 pull_coord1_dim = N N Y pull_coord1_rate= 0.0 pull_coord1_k = 800 pull_coord1_start = yes I would now be very interested why the curve does not become flat beyond some certain distance, but rather seems to increase in a linear fashion, though the distance between the pull groups is sufficiently large. Could this be related to entropic effects? Is there a way to have the PMF properly normalized? The force field here is GROMOS 53a6 with SPC water. Temperature is coupled to 310 K and pressure to 1 bar. Cutoffs are 1.4 nm, longe range ES are resolved with PME and DispCorr is set to EnerPress. Bonds are constrained with LINCS. The Protein is prevented from rotation by having three CA atoms restrained with FC 1000. Thank you very much, I appreciate any help and suggestions. Lukas -- 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 - choice of pull-coord?-dim
Dear GROMACS users, I am interested in the role of the mdp parameter pull-coord?-dim when sampling a particular umbrella window after having generated initial configurations for, say, the COM distance between two groups being the reaction coordinate. I know that these options can be controlled to restrict the actual pulling, say with geometry distance, to a subset of the pull vector components, for instance to enable aligment of the pull vector with the box dimensions. However, I do not understand its role when performing umbrella sampling along the reaction coordinate. I know that the pull-code then controls the COM distance between the pull groups with a (usually) harmonic potential, but what effect will pull-coord?-dim have? I observe different behavior for my toy system consisting of two methanol molecules in vacuum. With all components enables, I need to correct the PMF for entropic decrease in the PMF, since the methanol is sampled on a sphere with increasing radius. If only allowing one component, the PMF will be flat, but different values for delta G result. Also, in the US Tutorial by Justin, the US code uses: pull_coord1_dim = N N Y Is there any particular reason, not to set pull_coord1_dim = Y Y Y here? Would this setting also be justified? Since, as far as I understood the procedure, pulling is just there for generating the initial configurations and US is more or less independent of this. Many thanks in advance! Lukas -- 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.
