Re: [AMBER] scientific issue

From: Josh Berryman <>
Date: Wed, 10 Nov 2021 17:17:21 +0100

Absolutely! Breaking up an aggregate with some kind of detergent or
whatever can be slower than forming it was - possibly the detergent only
blocks re-attachment of monomers that have diffused off the aggregate by
themselves, for an example. You could try giving it hundreds of
microseconds on GPU, but if the kinetic timescale is milliseconds or days
then you will never see anything.

Form a hypothesis for the kinetic mechanism, and try to estimate pathways
and barrier heights by using classical nucleation theory. Once you have a
hypothesis for the reaction mechanism you can think about trying to test it
with simulation.

Really there are only a few possible processes, which you can think about
probing individually with some kind of steered MD:

1) Monomer 1 attachment
2) Monomer 2 attachment
3) aggregate internal rearrangement
4) monomer 1 structural change
5) monomer 2 structural change
x2 for reverses of each of the above


On Wed, 10 Nov 2021 at 17:05, David A Case <> wrote:

> On Wed, Nov 10, 2021, SOMA ROY wrote:
> >
> >Problem: I am simulating the aggregation of some small molecules (small
> >molecule-1). After the simulation, I am going to add another small
> >molecule (small molecules-2) to the nanoaggregates which may dissipate the
> >nanoaggregates as observed from the experimental data. Now, I have
> >performed the simulation of the small molecule-1 aggregation. When I have
> >added the small molecule-2 to the aggregates, it is clumping with the
> small
> >molecule-1. How should I simulate the dissipation of the small molecule-1
> >nanoaggregates after the addition of the small molecule-2?
> This might be a kinetic problem, that is takes a long time for molecule-2
> to
> dissipate the aggregates. It may also be a force-field problem: the system
> may favor nanoaggregates even when molecule-2 is present. Or, the
> experimental setup and that in the simulation may be different; are you
> sure
> your simulated concentrations are realistic?
> One thought: try starting with both molecule-1 and molecule-2 as monomers,
> and see if there is a difference in aggregation compared to the simulation
> where no molecule-2 molecules were present.
> This is a very complex problem, and it may take a lot of work to create a
> physically-realistic simulation. Don't lose sight of the fact that you
> want to learn something new from the simulations, and not just reproduce
> known experimental results. Even "failed" simulations may lead to novel
> insights.
> ...dac
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Received on Wed Nov 10 2021 - 08:30:03 PST
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