----- Original Message ----- From: ms <[email protected]> Date: Monday, October 18, 2010 8:23 Subject: [gmx-users] The trouble with dihedral restraints: frozen peptide backbones To: Discussion list for GROMACS users <[email protected]>
> Hi, > > It's a bit long but bear with me if you can. I'm getting quite > mad with this. Thanks :) > > Now. I am using Gromacs (4.0.7 currently) to create a custom > coarse-grained, no-solvent MD peptide model -one that contains > the backbone but has only C-alphas, no side chains. > > To enforce chirality in such a toy, I thought that a simple > (naive?) but functional idea could be that of enforcing a not- > too-hard and wide-bottomed dihedral restrain on the phi angle, > like that: > > [ dihedral_restraints ] > ; ai aj ak > al type label phi dphi kfac power > ; phi C'(n-1) - N - CA - C' > 3 > 5 7 8 1 1 -90 75 2 1 Try mdrun -debug on a short run. What does it have to say about the parameter values for this dihedral restraint? Likewise gmxdump -s on the .tpr (though you will have to search around for F_DIHRES among other things, probably). Mark > > so that the system is free to move in a large phi-angle space > without problems, but cannot go in the forbidden, symmetrical > glycine-like space. In testing, I set the force constant small > (10) so that the chain, even if with some difficulty, should be > able to bend and move by spending some energy in the "forbidden" > zones, if needed to achieve structure, etc. > > Now, the point is that *when* it works, it works quite well. But > sometimes -with "sometimes" being from 0% to 90% of times, > depending on details of what I am simulating- it totally > doesn't. That is: sometimes, starting from an extended > structure, the chain simply freezes. It is not static: it > wiggles a bit here and there, but it stays mostly extended. > Energies plots (g_energy output xvg's) are on average flat: that > is, they show the right noise for all components, but no > structure: nothing happens, for as much as 50 ns. > > Sometimes instead it works, and then you see that everything > works alright; the peptide structures, potential energy goes > down and down, etc.etc. > > There are no differences in minimization energies etc. from a > simulation that freezes and one that works. Moving the restraint > center doesn't help much. I *know* it's the restraints because > if I keep everything the same but I lower the force constant or > remove restraints altogether, the freezing bug happens no more - > but then I have little or no more chirality, of course. I have > the following further facts: > - It tends to happen more often for longer chains: 10 or 20- > residue long chains work often OK, but a 40-long chain is > difficult to get "right". > - It *never* happens, to my knowledge, if I put more than 1 > chain to cluster in the box. > - The Ramachandran plot of the extended frozen thing is "right", > meaning that it populates a reasonable (mostly beta) angle > space. During trajectory angles move quite a bit but stay in the > right (top-left) zone of the plot. > - "Good"-behaving simulation often start with a short "frozen" > stretch: then the dihedral restraint energy suddenly jumps to > some above noise positive value, to accomodate some bending I > guess, and all goes downhill from there. > - In frozen simulations, there's almost no LJ energy: the chain > does not self-interact. > > All of this, added to the apparent "randomness" of the > pathology, makes me think that the chain simply is stuck in a > situation where it has a too high barrier to properly bend -a > barrier which is not a "soft" one as the harmonic potential of > the restrain would make me think. This would explain why putting > more peptides and letting them bind together avoids the problem: > the potential energy of binding compensates for the bending when > you have more than one thing; but sometimes a single chain > cannot find itself to interact with, because it should bend > correctly to do so. > > And then, I read on the Gromacs website *this* > http://www.gromacs.org/Documentation/How-tos/Dihedral_Restraints > " 2. The manual is a bit unclear about whether this type of > dihedral restraint is stable for use near 180 degrees. Chris > Neale has found that everything appears to behave normally and > as expected over the entire range of dihedral angles including > 180 degrees. However, one must avoid the situation in which the > actual dihedral is close to 180deg away from the restrained dihedral." > > And I know that somehow the potential is discontinuous and/or > anyway not intended to be well-behaved everywhere: > http://www.mail-archive.com/[email protected]/msg12353.html > > "> On Tue, Feb 26, 2008 at 11:37 AM, David Mobley <[EMAIL > PROTECTED]> wrote: > > > The other way of putting what Mark said is that phi is > only meaningful on some range (-pi to pi, or 0 to 2pi, depending > on how you define it) > > > and so what you require is that the potential be > harmonic for the > > > region in which phi is meaningful. You don't care what > happens outside that. Or, in this case, you handle the issue by > mapping phi values outside the allowed range back into > that allowed range." > > (I don't get what does it mean to "map back" phi values, by the way). > > I am no MD expert, so maybe my hypothesis is totally off, but I > am reasonably sure that either I do not understand correctly how > dihedral restraints work, or I am suffering by the discontinuity > of the way the potential is implemented (Or both). I would like > to know: > - How can I try to understand in full what is going on > - If my diagnosis sounds right, how can I start to correct the > problem.- If the problem is my naive approach to chirality, any > suggestion is welcome. > > Thanks A LOT if you've been patient enough to read until here! > And thanks even *more* if you can help! > > Yours truly, > Massimo > -- > gmx-users mailing list [email protected] > http://lists.gromacs.org/mailman/listinfo/gmx-users > Please search the archive at > http://www.gromacs.org/Support/Mailing_Lists/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/Support/Mailing_Lists
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