The distortion was occuring because my position restraint potential was too weak. Increasing the force constant keeps the base in the right conformation.
I believe my topology is correct, but it seems that turning off the VdW parameters causes the base to distort. I will look into this more. Also, even with sc_alpha=0.5, I'm still experiencing this weird "freezing" when lambda=1.0. The trajectory proceeds normally for about 2.1 ns, then all of a sudden all motion freezes and the atoms simply vibrate about their "equilibrium positions". Any other ideas what might cause this? Thanks, Bob On Jan 21, 2008 3:39 AM, Maik Goette <[EMAIL PROTECTED]> wrote: > Robert > > A value for alpha of 0.5 should work, although I tested some different > alphas with different test systems and I have to say, that a proper > value can be between 0.2 and 0.7 depending on the system itself. > The distortion, you describe is really strange. I calculated DNA and > single bases a lot and never saw something like that. Even a fully > "dummy-base" is stable, if your topology is correct. The bonded terms > are sufficient to keep it in the right conformation. > Are you sure, your position restrains in the topology are used with the > correct structure file? > > Maybe, I should also mention, that, especially with such large > perturbations as a full DNA-base, you should split your topology into 2, > where you switch off the QQ hardcore and the VdW softcore in two steps. > > Regards > > Maik Goette, Dipl. Biol. > Max Planck Institute for Biophysical Chemistry > Theoretical & computational biophysics department > Am Fassberg 11 > 37077 Goettingen > Germany > Tel. : ++49 551 201 2310 > Fax : ++49 551 201 2302 > Email : mgoette[at]mpi-bpc.mpg.de > mgoette2[at]gwdg.de > WWW : http://www.mpibpc.gwdg.de/groups/grubmueller/ > > > Robert Johnson wrote: > > > Thank you David and Maik for your detailed replies. Yes, I am trying > > to obtain an absolute free energy of binding. My thermodynamic cycle > > is: > > > > NT+DNA(adsorbed) -> NT+ DNA(desorbed) (obviously this is not the one > > that I'm obtaining with the alchemic method) > > > > Thus, the one I'm using in the simulation is: > > > > Water + NT + DNA(adsorbed) -> Water + NT + nothing (DNA dissapears) > > Water + DNA -> Water + nothing > > > > Any suggestions about this? I will check out your recent publications. > > > > I believe my topology is properly formatted. I wasn't expecting the > > large distortions because I was using position restraints. Thus, I was > > expecting the base to remain in about the same geometry. Perhaps I > > will increase the force constant for the restraining potential. > > > > I am going to repeat some of these computations using sc_alpha=0.5. > > > > Thanks for your help. > > Bob > > > > On Jan 17, 2008 2:24 PM, David Mobley <[EMAIL PROTECTED]> wrote: > >> Robert, > >> > >>> I'm computing the free energy of binding of a DNA base on a carbon > >>> nanotube. I think it's a pretty simple calculation and I'm proceeding > >>> in a very standard way. This is what I'm doing: > >> An absolute free energy? This isn't necessarily straightforward -- > >> there are a lot of wrinkles. Some of my recent work has some > >> discussions if this if it's helpful. > >> > >>> I have the optimal orientation of the base on the nanotube. I'm > >>> constraining the positions of the base atoms with a soft harmonic > >>> potential. > >> OK, that's a good idea for standard state reasons (see the 2003 > >> Boresch paper) among other things. > >> > >>> I then am running two different FEP calculations: one where I turn off > >>> the charges on the base atoms and a second where I then turn off all > >>> the lennard-jones parameters for the base atoms. For each of these I > >>> use the following: > >>> delta_lambda = 0 > >>> sc_alpha = 0.7 > >>> sc_power = 1 > >>> sc_sigma = 0.3 > >>> > >>> I run a series of trajectories at constant lambda values from 0 to 1. > >> OK. I have some information posted on what I think the best settings > >> are for these on alchemistry.org, especially at > >> http://www.alchemistry.org/wiki/index.php/Best_Practices. It is still > >> in progress but may be somewhat helpful. I doubt this is the source of > >> your problems though, although I prefer a sc_alpha = 0.5 which may > >> improve the situation somewhat. > >> > >>> However, I notice some problems with the trajectories when I turn off > >>> the LJ parameters. As lambda is varied from 0 to 1, it seems that the > >>> position restraints no longer are being applied. Additionally, the DNA > >>> base geometry starts to become severely distorted at lambda values > >>> greater than about 0.6. This happens despite the fact that I am not > >>> perturbing the internal bonded interactions of the base. Here is a > >>> sample of my topology (included just the first line of each section): > >> Hm, on the position restraints, depending on your version of gromacs > >> you may need to additionally specifiy the B state position restraints, > >> else these may be assumed to be zero. I believe you can do this by > >> adding additional columns in your posre.itp that give the B state > >> parameters. > >> > >> In terms of distortion, it's not clear to me why you think the > >> molecule should *not* be distorted once you turn off the LJ > >> interactions (which includes internal LJ interactions). The bonded > >> parameters (especially torsions) are of course derived after LJ > >> parameters are already fitted, in most cases, so they only can be > >> relied on to give meaningful conformations when the LJ interactions > >> are on. The beauty of the thermodynamic cycle approach, though, is > >> that you can (at least in principle) get correct binding free energies > >> even if your molecule of interest samples wacky, artificial > >> conformations when it's noninteracting. > >> > >>> Also, I am experiencing additional problems when lambda=1. After about > >>> 2ns, all the motion in the system begins to freeze and all the atoms > >>> simply vibrate about a fixed position. Soon after that the simulation > >>> crashes. > >> My experience has been that sc-alpha = 0.7 can lead to a fairly steep > >> dV/dlambda and some large forces near lambda=1, which is why I > >> recommend sc-alpha = 0.5. This parameter is actually fairly sensitive. > >> This *could* lead to crashes, but I don't know about > >> freezing/vibrating. > >> > >> Let me know if this helps. > >> > >> Best wishes, > >> David Mobley > >> UCSF > >> http://www.dillgroup.ucsf.edu/~dmobley > >> > >>> Can anyone comment on what's going on here? > >>> Thanks, > >>> Bob Johnson > >>> _______________________________________________ > >>> gmx-users mailing list gmx-users@gromacs.org > >>> http://www.gromacs.org/mailman/listinfo/gmx-users > >>> Please search the archive at http://www.gromacs.org/search before posting! > >>> Please don't post (un)subscribe requests to the list. Use the > >>> www interface or send it to [EMAIL PROTECTED] > >>> Can't post? Read http://www.gromacs.org/mailing_lists/users.php > >>> > >> _______________________________________________ > >> gmx-users mailing list gmx-users@gromacs.org > >> http://www.gromacs.org/mailman/listinfo/gmx-users > >> Please search the archive at http://www.gromacs.org/search before posting! > >> Please don't post (un)subscribe requests to the list. Use the > >> www interface or send it to [EMAIL PROTECTED] > >> Can't post? Read http://www.gromacs.org/mailing_lists/users.php > >> > > _______________________________________________ > > gmx-users mailing list gmx-users@gromacs.org > > http://www.gromacs.org/mailman/listinfo/gmx-users > > Please search the archive at http://www.gromacs.org/search before posting! > > Please don't post (un)subscribe requests to the list. Use the > > www interface or send it to [EMAIL PROTECTED] > > Can't post? Read http://www.gromacs.org/mailing_lists/users.php > > > > . > > > _______________________________________________ > gmx-users mailing list gmx-users@gromacs.org > http://www.gromacs.org/mailman/listinfo/gmx-users > Please search the archive at http://www.gromacs.org/search before posting! > Please don't post (un)subscribe requests to the list. Use the > www interface or send it to [EMAIL PROTECTED] > Can't post? Read http://www.gromacs.org/mailing_lists/users.php > _______________________________________________ gmx-users mailing list gmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to [EMAIL PROTECTED] Can't post? Read http://www.gromacs.org/mailing_lists/users.php