Thanks for the explanation on the Quasiharmonic entropy calculation.
I have too many trajectories to calculation and the system is too large, in my case pruning the structure is necessary for nmode, and as a even faster alternative a single average (no pruning) was worth trying-the average structure is distorted, but then I thought there’s the minimization that restores things, and that as long as the frames all come from a single energy minimum (no major changes between each other), it may be ok.
The results I got on one test from 8 separate frames vs average frame from 8 was total entropy 3065 vs 3064, which was very good, though the binding delta was larger in difference, -69 vs -59.
> On Mar 28, 2021, at 3:43 PM, David A Case <david.case.rutgers.edu> wrote:
>
> On Sun, Mar 28, 2021, Liao wrote:
>>
>> So from what I see, MMPBSA.py is calling cpptraj and seems to be generating
>> an average frame over all the selected frames, and doing the quasi-harmonic
>> calculation on that single frame.
>
> The average structure is an intermediate quantity: after is computed, the
> covariance matrix is computed as sigma_ij = <(x_i - xav_i)(x_j - xav_j)>,
> and the average is over all the frames you ask cpptraj to use. After that,
> the average structure is discarded, and the effective forces determined from
> the sigma_ij covariance matrix. Depending on the size and flexibility of
> the system, quasi-harmonic results can be difficult to converge.
>
>>
>> I guess now I’ll try to first manually generate an average in cpptraj, and
>> use that single frame as the nmode calculation input to see what I get.
>
> This would not make good sense: the average structure is often a distorted
> one, and is not "representative" of the ensemble. Try doing a normal mode
> calculation on a dozen or so snapshots, and see how much variation you are
> getting. Then check the results using 12 snapshots vs. using 24, etc.
>
> Here is an old, but still revelant study of this subject:
>
> %A H. Gohlke
> %A D.A. Case
> %T Converging Free Energy Estimates: MM-PB(GB)SA Studies on the Protein-Protein Complex Ras-Raf
> %J J. Comput. Chem.
> %V 25
> %P 238-250
> %D 2004
>
> ....dac
>
>
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Received on Mon Mar 29 2021 - 11:30:02 PDT
