Thank you both!
Yes, I was saving frames every 20 femtoseconds in order to obtain that many
frames (I had 5 ns of equilibrated trajectory I wanted to use). It seems
like that is bad because the frames are not decorrelated. What exactly is a
good time step for entropy calculation? Around 1 ps?
One more question: If I use only the alpha carbons, what do I do with the
ligand, which is free arginine? If I represent it just by one atom, its
alpha atom, it seems a little weird. Should I include all of the arginine's
atoms both in the compex trajectory and the arginine trajectory? Or does it
not make a big difference what I do with the arginine since its entropy
will be small compared to that of the complex and receptor?
Best,
Laura
On Tue, Apr 28, 2015 at 7:19 AM, Hannes Loeffler <Hannes.Loeffler.stfc.ac.uk
> wrote:
> Hi,
>
> One more note: if you look at the formula for the vibrational entropy
> you will see that this function falls of quite sharply with increasing
> frequencies. Hydrogen vibrations obtained from normal mode have
> essentially no influence on the final entropy despite their, typically,
> relative high proportion to all other normal modes. Just look at the
> output from e.g. nmode to see this in action.
>
> When you do quasi-harmonic analysis/PCA you are typically looking at the
> large global motions i.e. low frequency modes. Hydrogens should have
> very little influence on this, maybe you could see some effect from
> C-alpha only versus heavy-atoms only (i.e. including the side-chains).
> Maybe worth a try to get a feel for it.
>
> Cheers,
> Hannes.
>
>
> On Tue, 28 Apr 2015 12:51:46 +0200
> Josh Berryman <the.real.josh.berryman.gmail.com> wrote:
>
> > >>I was thinking if maybe I could reduce the number of frames needed
> > >>for
> > the quasi-harmonic
> > >>calculation by removing all hydrogen atoms from the trajectory.
> >
> > Absolutely, entropy from things like methyl-group rotation is probably
> > unimportant and not very well captured by this method anyway. It is
> > not unheard-of to throw away everything except the C-alphas,
> > especially if memory for the diagonalisation becomes a problem.
> >
> > Also, try doing a convergence analyisis of what happens to the
> > entropy as you run the calculation on increasingly longer trajectory
> > segments, it should follow a power law which you can extrapolate to
> > t=infinity. This rather obscure maths paper gives an explanation of
> > why it works, plus links back to the simulation papers where the
> > approach was discovered:
> >
> > Title = {Statistical inference for functions of
> > the covariance matrix in the stationary Gaussian time-orthogonal
> > principal components model},
> > Author = {Dryden, IanL. and Kume, Alfred and Le,
> > Huiling and Wood, AndrewT.A.},
> > Journal = {Annals of the Institute of Statistical
> > Mathematics},
> > Year = {2010},
> >
> >
> >
> > >>I started an MMPBSA calculation using these three trajectories and
> > >>using all 250 000 frames and at the rate at which the frames are
> > >>being processed right now, I anticipate at least 3-4 days will be
> > >>spent just on the GB calculations
> >
> > The number of nanoseconds might be more pertinent than the number of
> > frames here. Collecting a PE snap every 2 femtoseconds would
> > certainly be a bit excessive, as the decorrelation time of your
> > energies is rather longer than this.
> >
> > >>restarting MMPBSA...
> >
> > sorry, never tried
> >
> > Josh
> >
> >
> >
> > On 27 April 2015 at 05:35, Laura Tociu <ltociu.princeton.edu> wrote:
> >
> > > Dear Amber users,
> > >
> > > I am attempting to calculate the entropic contribution to the
> > > binding energy of a very large system and previously I had thought
> > > about truncating the system and using NMode but eventually decided
> > > against it because the protein has a very obvious correlated motion
> > > of its monomers and upon binding that motion is almost lost so the
> > > quasi-harmonic approximation would probably be pertinent to this
> > > case.
> > >
> > > The number of atoms being 6000 + I need at least 18 000 frames for
> > > the quasi-harmonic approximation. So I now have three separate
> > > trajectories (one of the protein, one of the complex and one of the
> > > ligand -- I wanted to use separate trajectories precisely because
> > > upon binding the motion of the protein changes), each having 250
> > > 000 frames.
> > >
> > > I started an MMPBSA calculation using these three trajectories and
> > > using all 250 000 frames and at the rate at which the frames are
> > > being processed right now, I anticipate at least 3-4 days will be
> > > spent just on the GB calculations, and I can't estimate how much
> > > the entropy calculation will take and whether everything will run
> > > smoothly or not from now on.
> > >
> > > Since obtaining this entropy is a little time-sensitive now, I was
> > > thinking if maybe I could reduce the number of frames needed for
> > > the quasi-harmonic calculation by removing all hydrogen atoms from
> > > the trajectory. This would reduce the number of frames needed by
> > > roughly a half. I was thinking about doing two MMPBSA calculations:
> > > one using a trajectory with all of the hydrogens present, from
> > > which I would derive the intramolecular energy and the solvation
> > > energy and one using a trajectory that is free of hydrogens, from
> > > which I would simply derive the entropy. I recall reading about
> > > something similar in an article but am not sure I remember
> > > correctly. Is this a valid procedure?
> > >
> > > If not could someone tell me if an MMPBSA calculation can be
> > > restarted if it dies for whatever reason and how? I know there is
> > > an option to use the existing input files, but I am not sure if
> > > this means that the script will pick up where it left off if it
> > > died in the middle of frame processing for example.
> > >
> > > Thank you!
> > >
> > > Laura
> > > _______________________________________________
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> > > http://lists.ambermd.org/mailman/listinfo/amber
> > >
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>
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Received on Tue Apr 28 2015 - 13:00:06 PDT
