Re: [AMBER] Free energy landscape

From: anu chandra <>
Date: Thu, 27 Nov 2014 17:14:44 +0530

Thanks for the immediate reply.

On Wed, Nov 26, 2014 at 10:42 PM, Carlos Simmerling <> wrote:

> You haven't given us much info. First, you need to ensure that these basins
> are all reliable and reproducible. Free energies from straight md are
> notoriously unreliable and it's easy to over interpret the results. Make
> sure you can physically justify them as well and they are not just noise.
> To get back to your question, you ask about the "initial stage of
> simulation". What exactly takes place in this simulation? What are you
> doing? What do you mean "change while ligand binding"? Are you forcing
> binding to occur?
One way to get the insight you're looking for is to map the time dependence
> of the projection of each snapshot onto the pca modes. That way you can map
> basins to structures. Explaining what's going on would then take some
> structural biology insight, knowledge of your specific system, and most
> likely design of followup data analysis to confirm that what you see in the
> snapshots is actually a well sampled property in the MD run and not just an
> artifact of looking at a subset of the snapshots. Then you would use this
> information to compare to experimental data, keeping in mind all of the
> potential weaknesses of your simulation. Ideally you will make specific
> predictions that are then confirmed through experiments.

In the apo system, ligand binding pocket of the protein shift between open
and closed state, where in ligand bound system the pocket get locked in its
closed state. It seems like the closed and open state have very narrow
energy barrier as it can be sampled during all-atom classical MD. In apo
simulation, the free energy landscape from principal modes shows six
low-energy basins and mapped structures from different basins could able to
explain the closed and open states. However, I would like to see what could
be the possible direction of exploring these different minima in the
landscape during simulation?

Many thanks


On Nov 26, 2014 6:07 AM, "anu chandra" <> wrote:
> > Dear Amber users,
> >
> > I am working with MD simulation of protein -ligand interaction. In order
> to
> > get information about subtle change in protein while ligand binding, I
> have
> > carried out principal component analysis (PCA). I have also drawn the
> free
> > energy landscape using PC1 and PC2, which came up with five low-energy
> > basins. is there a way to identify which basin will be encountered at the
> > initial stage of simulation?
> >
> > Many thanks,
> >
> > Anu
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> >
> >
> >
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Received on Thu Nov 27 2014 - 04:00:03 PST
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