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OK,<br>I will try to increase the distances of the c.o.m of both molecules to eliminate any contact between them, adding more windows.<br>Thanks a lot for your help!<br>Best wishes,<br>Rebeca.<br><br><div>> Date: Wed, 22 Jun 2011 11:51:36 -0400<br>> From: jalemkul@vt.edu<br>> To: gmx-users@gromacs.org<br>> Subject: Re: [gmx-users] restraints in PMF (Justin's tutorial)<br>> <br>> <br>> <br>> Rebeca García Fandiño wrote:<br>> > Thanks a lot for your quick answer!<br>> > I think they are separated enough, however my monomers are cyclic (like <br>> > discs); I start with a parallel conformation between then, but along the <br>> > Umbrella simulation, both of them rotate and approach.<br>> > If I do not use restraints, how could I avoid the rotation?<br>> > <br>> <br>> You don't. Why wouldn't two molecules rotate freely in solution when binding or <br>> unbinding? It seems like completely natural behavior. Even in simple systems <br>> of protein-ligand association, part of the binding energy is the entropic <br>> restriction of the ligand into a certain binding-competent pose. Why wouldn't <br>> that happen here? Sounds like an artificial notion to me.<br>> <br>> -Justin<br>> <br>> > I am using the following md_umbrella.mdp:<br>> > <br>> > title = Umbrella pulling simulation<br>> > define =<br>> > define =<br>> > ; Run parameters<br>> > integrator = md<br>> > dt = 0.002<br>> > tinit = 0<br>> > nsteps = 500000 ; 1 ns<br>> > nstcomm = 10<br>> > ; Output parameters<br>> > nstxout = 5000 <br>> > nstvout = 5000<br>> > nstfout = 5000<br>> > nstxtcout = 5000 <br>> > nstenergy = 5000<br>> > ; Bond parameters<br>> > constraint_algorithm = lincs<br>> > constraints = all-bonds<br>> > continuation = yes<br>> > ; Single-range cutoff scheme<br>> > nstlist = 5<br>> > ns_type = grid<br>> > rlist = 1.4<br>> > rcoulomb = 1.4<br>> > rvdw = 1.4<br>> > ; PME electrostatics parameters<br>> > coulombtype = PME<br>> > fourierspacing = 0.12<br>> > fourier_nx = 0<br>> > fourier_ny = 0<br>> > fourier_nz = 0<br>> > pme_order = 4<br>> > ewald_rtol = 1e-5<br>> > optimize_fft = yes<br>> > ; Berendsen temperature coupling is on in two groups<br>> > Tcoupl = Nose-Hoover<br>> > tc_grps = r_1_r_2 CL3<br>> > tau_t = 0.5 0.5<br>> > ref_t = 300 300<br>> > ; Pressure coupling is on<br>> > Pcoupl = Parrinello-Rahman<br>> > pcoupltype = isotropic<br>> > tau_p = 1.0<br>> > compressibility = 4.5e-5<br>> > ref_p = 1.0<br>> > ; Generate velocities is off<br>> > gen_vel = no<br>> > ; Periodic boundary conditions are on in all directions<br>> > pbc = xyz<br>> > ; Long-range dispersion correction<br>> > DispCorr = EnerPres<br>> > ; Pull code<br>> > pull = umbrella<br>> > pull_geometry = distance<br>> > pull_dim = N N Y<br>> > pull_start = yes<br>> > pull_ngroups = 1<br>> > pull_group0 = r_1<br>> > pull_group1 = r_2<br>> > pull_init1 = 0<br>> > pull_rate1 = 0.0<br>> > pull_k1 = 1000 ; kJ mol^-1 nm^-2<br>> > pull_nstxout = 1000 ; every 2 ps<br>> > pull_nstfout = 1000 ; every 2 ps<br>> > <br>> > Thanks a lot again for your help.<br>> > <br>> > Best wishes,<br>> > <br>> > Rebeca.<br>> > <br>> > <br>> > > Date: Wed, 22 Jun 2011 10:53:16 -0400<br>> > > From: jalemkul@vt.edu<br>> > > To: gmx-users@gromacs.org<br>> > > Subject: Re: [gmx-users] restraints in PMF (Justin's tutorial)<br>> > ><br>> > ><br>> > ><br>> > > Rebeca García Fandiño wrote:<br>> > > > Hello,<br>> > > > I am trying to obtain the PMF from Umbrella Sampling of the process of<br>> > > > separating two monomers of a dimer, following Justin 's tutorial<br>> > > > <br>> > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html<br>> > > ><br>> > > > I have done the Umbrella Sampling simulations without using any<br>> > > > restraints in any of the monomers, however, I can see that they <br>> > move and<br>> > > > gyrate so that although the c.o.m are separated from each other, there<br>> > > > are parts of both interacting, in such way that they are not separated<br>> > > > as they should be.<br>> > > ><br>> > > > Would it be correct if I apply restraints to both monomers in all the<br>> > > > Umbrella Sampling simulations?. I have seen that in Justin's tutorial<br>> > > > they applied restraints to one of the chains, but in my case I think I<br>> > > > will need to restrain both of the units. Would that be correct for the<br>> > > > PMF calculation?<br>> > > ><br>> > ><br>> > > There are no position restraints applied during the umbrella sampling<br>> > > simulations. They are unnecessary. The umbrella potential is itself a<br>> > > restraint to maintain COM separation.<br>> > ><br>> > > If parts of your proteins are interacting, you simply haven't fully <br>> > separated<br>> > > your monomers and you need to create configurations with greater COM <br>> > separation.<br>> > > If you apply position restraints to fit some notion that your monomers<br>> > > shouldn't interact at certain distances, then you're applying an <br>> > unnatural (and<br>> > > potentially incorrect) bias, causing the PMF to converge incorrectly.<br>> > ><br>> > > -Justin<br>> > ><br>> > > > Thanks a lot in advance.<br>> > > ><br>> > > > Rebeca.<br>> > > ><br>> > > > > Date: Mon, 20 Jun 2011 17:03:56 -0400<br>> > > > > From: jalemkul@vt.edu<br>> > > > > To: regafan@hotmail.com<br>> > > > > CC: gmx-users@gromacs.org<br>> > > > > Subject: Re: doubt about your Umbrella Sampling tutorial<br>> > > > ><br>> > > > ><br>> > > > ><br>> > > > > Rebeca García Fandiño wrote:<br>> > > > > > Dear Justin,<br>> > > > > > my name is Rebeca and I am a postdoctoral student in Santiago de<br>> > > > > > Compostela University. Sorry for disturbing you to your personal<br>> > > > mail, I<br>> > > > > > have tried to post to the Gromacs-list first, but I did not get <br>> > any<br>> > > > answer.<br>> > > > ><br>> > > > > I was traveling and not paying much attention to messages across the<br>> > > > list. I<br>> > > > > will CC this reply to the list in the hopes that it is useful to<br>> > > > others, as well.<br>> > > > ><br>> > > > > > I am trying to obtain the PMF from Umbrella Sampling of the <br>> > process of<br>> > > > > > separating two monomers of a dimer, following your tutorial, and I<br>> > > > have<br>> > > > > > a pair of doubts:<br>> > > > > ><br>> > > > > > 1)In this tutorial the generation of configurations is done <br>> > using a<br>> > > > .mdp<br>> > > > > > file for pulling one chain from another, but is it possible to<br>> > > > generate<br>> > > > > > the configurations for Umbrella Sampling "by hand", I mean,<br>> > > > changing the<br>> > > > > > z coordinate of the monomer I want to move, then solvating and then<br>> > > > > > minimizing these configurations? Is there any problem with this<br>> > > > protocol<br>> > > > > > for the obtaining of the configurations?<br>> > > > > ><br>> > > > ><br>> > > > > No problem at all. The tutorial is but one possible method.<br>> > > > ><br>> > > > > > 2) I have noticed that you use restraints in the md_umbrella.mdp<br>> > > > for the<br>> > > > > > fixed chain. Is that correct? I can understand the restraints <br>> > in the<br>> > > > > > pulling simulations for generate starting configurations, but <br>> > once you<br>> > > > > > have the configurations, is is necessary to restrain one part <br>> > of the<br>> > > > > > system?<br>> > > > > ><br>> > > > ><br>> > > > > Not usually. The tutorial presents a special case.<br>> > > > ><br>> > > > > > Thanks a lot in advance for your help with this topic, and <br>> > thank you<br>> > > > > > very much also for publishing this interesting tutorial. There was<br>> > > > > > nothing useful until that for Umbrella Sampling with Gromacs <br>> > 4.0, so I<br>> > > > > > think it is more than wellcome for all Gromacs users!<br>> > > > ><br>> > > > > Glad they're useful :)<br>> > > > ><br>> > > > > -Justin<br>> > > > ><br>> > > > > > Best wishes,<br>> > > > > > Rebeca.<br>> > > > > ><br>> > > > > > Dr. Rebeca García Fandiño<br>> > > > > > Department of Organic Chemistry and Center for Research in <br>> > Biological<br>> > > > > > Chemistry<br>> > > > > > and Molecular Materials<br>> > > > > > Santiago de Compostela University<br>> > > > > > E-15782 Santiago de Compostela (Spain)<br>> > > > > > e-mail: rebeca.garcia.fandino@usc.es<br>> > > > > > Phone: 34-981563100 ext 15760<br>> > > > > ><br>> > > > > ><br>> > > > > ><br>> > > > > ><br>> > > > > ><br>> > > > > ><br>> > > > > ><br>> > > > ><br>> > > > > --<br>> > > > > ========================================<br>> > > > ><br>> > > > > Justin A. Lemkul<br>> > > > > Ph.D. Candidate<br>> > > > > ICTAS Doctoral Scholar<br>> > > > > MILES-IGERT Trainee<br>> > > > > Department of Biochemistry<br>> > > > > Virginia Tech<br>> > > > > Blacksburg, VA<br>> > > > > jalemkul[at]vt.edu | (540) 231-9080<br>> > > > > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin<br>> > > > ><br>> > > > > ========================================<br>> > > ><br>> > ><br>> > > --<br>> > > ========================================<br>> > ><br>> > > Justin A. Lemkul<br>> > > Ph.D. Candidate<br>> > > ICTAS Doctoral Scholar<br>> > > MILES-IGERT Trainee<br>> > > Department of Biochemistry<br>> > > Virginia Tech<br>> > > Blacksburg, VA<br>> > > jalemkul[at]vt.edu | (540) 231-9080<br>> > > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin<br>> > ><br>> > > ========================================<br>> > > --<br>> > > gmx-users mailing list gmx-users@gromacs.org<br>> > > http://lists.gromacs.org/mailman/listinfo/gmx-users<br>> > > Please search the archive at <br>> > http://www.gromacs.org/Support/Mailing_Lists/Search before posting!<br>> > > Please don't post (un)subscribe requests to the list. Use the<br>> > > www interface or send it to gmx-users-request@gromacs.org.<br>> > > Can't post? Read http://www.gromacs.org/Support/Mailing_Lists<br>> <br>> -- <br>> ========================================<br>> <br>> Justin A. Lemkul<br>> Ph.D. Candidate<br>> ICTAS Doctoral Scholar<br>> MILES-IGERT Trainee<br>> Department of Biochemistry<br>> Virginia Tech<br>> Blacksburg, VA<br>> jalemkul[at]vt.edu | (540) 231-9080<br>> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin<br>> <br>> ========================================<br>> -- <br>> gmx-users mailing list gmx-users@gromacs.org<br>> http://lists.gromacs.org/mailman/listinfo/gmx-users<br>> Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting!<br>> Please don't post (un)subscribe requests to the list. Use the <br>> www interface or send it to gmx-users-request@gromacs.org.<br>> Can't post? Read http://www.gromacs.org/Support/Mailing_Lists<br></div> </div></body>
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