Re: [AMBER] Reweighting aMD conformations

From: Charo del Genio <>
Date: Tue, 13 Jul 2021 14:30:48 +0100

On 13/07/2021 13:54, Matthew Guberman-Pfeffer wrote:
> Dear Amber Community,
> I performed an aMD simulation of a fairly large protein complex, and I only now noticed the comment in the tutorial "For larger proteins with more than 100 residues, the energetic noise would be too high for accurate reweighting” ( <>). I wanted to run MM-GBSA on snapshots from the aMD simulation to assess the binding interaction of the protein domains, but I’m not sure if or how the results should be re-weighted. I’d greatly appreciate any suggestions.
> Best regards,
> Matthew

Hi Matthew,
        in my experience, I found that even with short peptides of 16 amino acids, one needs to be very very careful.

So, first of all, my suggestion is to use the smallest possible boost that allows you to access the transition you are interested in studying. However, even doing so, it is highly likely that you will
have some weights that are quite high, and higher than the others. This is practically certain to happen if you have a large protein complex, as you describe. In turn, this means that the algorithm
you use for the reweighting has to be carefully written, to avoid various numerical instabilities that can occur. Currently, I am working exactly on such a simulation, and I wrote a code that uses
MPFR (on top of GMP), so I can choose the precision I want in the calculation. The averaging itself is done by using logarithmic sums and a few other such tricks.

One other thing that can help is to try and use some approximation, as suggested in McCammon's paper (JCTC 10, 2677, 2014); note, however, that there is a typo in some equations there, so be careful.
Obviously, a well-characterized distribution of the weights makes things substantially easier, so, if you can, try to use GaMD.

Another suggestion is to subtract the lowest weight from all weights being used in the same ensemble, since this would result is the same multiplicative factor appearing in both the numerator and the
denominator of the reweighing equation, thereby cancelling each other out. Once more, though, be careful in doing this, as you don't want to end up subtracting numbers in the wrong place (the key in
the previous sentence is "in the same ensemble").

I hope this helps. If you have more questions, I'm happy to discuss things more.



Dr. Charo I. del Genio
Senior Lecturer in Statistical Physics
Applied Mathematics Research Centre (AMRC)
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Received on Tue Jul 13 2021 - 07:00:02 PDT
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