Re: [AMBER] question

From: Jason Swails <>
Date: Wed, 29 Jan 2014 08:37:08 -0500

On Mon, 2014-01-27 at 13:04 +0000, . mirage wrote:
> Hi amber user'sin order to study a comlexes type hote:invited 1:1 and
> 2:1 by calculating mmpbsa energy I chose one type on hote molecule (H)
> and two types of guest (A or B). we have then H>A, H>B, H>AA and H>BB
> For each type of complex, the guest B has the most stable orientations
> (minimum deltaG), but it has also some stable orientations A than B.
> My question is, what we say that B is more stable than A (on comparing
> only the orientation which have the minimum delta G ignoring some more
> stable orientation A than B.Thank's in advance for all reponse.

I'm not sure I understand the question. It seems that you have a host
that has two binding sites that can bind one of two guests; A or B. It
seems that the host can bind with either one or two of the guests, but
not one of each guest (i.e., not H>AB or H>BA), presumably because they
are never mixed together, I'm not sure. You ran molecular dynamics (I
am assuming) on these complexes and then performed MM/PBSA analyses on
the trajectories and got energies.

An important distinction: a single orientation is NOT a Delta G. Free
energies are ensemble averages over a Boltzmann-weighted distribution.
Simply discarding snapshots because they don't fit your expectations is
not a good approach. If you want to make some comparison of stability,
it is not the "lowest energy" snapshots you should be comparing, it is
the full ensemble averages.

If you have not run molecular dynamics simulations to generate the
snapshots you used for MM/PBSA and instead used something like docking
poses you got from some docking program then this is different. Docking
does not generate a proper Boltzmann-weighted distribution so you can
never be quite sure how to weight each orientation. In this case you
may be able to make an argument to discard unfavorable poses, but
ultimately such choices will be based on subjective evaluations and


Jason M. Swails
Rutgers University
Postdoctoral Researcher
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Received on Wed Jan 29 2014 - 06:00:06 PST
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