OK sir. Thank you very much for the suggestions.
One more doubt came from your reply
The output obtaining from entropy calculation using nmode; Its TdeltaS or
-TdeltaS ?
On Thu, May 12, 2016 at 11:20 PM, Jason Swails <jason.swails.gmail.com>
wrote:
> On Thu, May 12, 2016 at 12:26 AM, Mary Varughese <maryvj1985.gmail.com>
> wrote:
>
> > Sir,
> >
> > I am attaching herewith the output i got from single trajectory approach:
> > Here deltaG(= -15.91-(-22.43=6.52 a +ve value). As you could see
> especially
> > entropy varies much. Taking an average value does'nt seem to be ideal.
> >
>
> I don't know what you mean by "doesn't seem to be ideal". Taking an
> average is what you should be doing according to the theory behind MM/PBSA
> -- the snapshots are already sampled according to a Boltzmann distribution,
> so the Boltzmann weighting is built into the average. That said, the
> approximation used to compute entropy makes a lot of assumptions that may
> not hold up, and its reliance on rigorous minimization for normal mode
> calculations (which is difficult to do for large biomolecules) will likely
> result in potentially noisy data. After all, the most sensitive eigenmodes
> of the Hessian are the low-frequency modes, which also contribute the most
> to the entropy. That's why the standard deviations of the -TS term are so
> much larger than the other terms for the single-trajectory binding results.
>
>
>
> >
> > And i need to clear one thing about multiple trajectory.
> > step 1: run three long separate trajectories say a 50 ns each.
> > step 2:................
> > doubt : usually in single trajectory approach if we create say
> 3
> > snapshots;
> >
> > rec1: lig1: cmplx1==> deltaPB1 and TdeltaS1
> > rec2: lig2: cmplx2==> deltaPB2 and TdeltaS2
> > rec3: lig3: cmplx3==> deltaPB3 and TdeltaS3
> >
> > PB total= average(PB1,PB2,PB3); TdeltaS total= average(TS1,TS2,TS3);There
> > is a correspondence between rec, lig and cmplx
> >
> > In multiple trajectories there is nothing, I may never get a
> > correspondence.
> > I must be missing something in the way doing multiple trajectory
> approach.
> > It should be like Find the energy of rec, lig and cmplx for each
> > trajectory(for the full length of simulation) separately and then find
> the
> > difference at the end only. Isnt?
> > I really dont understand the logic in there.
> >
>
> I recommend going to the literature describing the MM/PBSA protocol (start
> from the MMPBSA.py reference and mine references from there and from the
> Amber manual). Then, as the manual suggests, make sure you can run MM/PBSA
> analyses *by hand* (i.e., without using either mm_pbsa.pl or MMPBSA.py) to
> make sure you understand what is being done at each step. Many of your
> questions would be easily answered by an understanding of the underlying
> theory behind MM/PBSA, and such an understanding will undoubtedly help
>
> you apply this methodology effectively now and in the future.
>
> HTH,
> Jason
>
> --
> Jason M. Swails
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Received on Thu May 12 2016 - 21:30:03 PDT
