Hi Kat,
My experience with accelerated MD is that indeed the secondary structure of
a protein can easily become distorted (especially helices). So with AMD,
you might end up exploring regions of the energy landscape you are not
interested in, for example the partial unfolding of your protein.
It is very likely that this is due to the fact that your parameters lead to
an acceleration that is a bit too aggressive.
It is a bit of an art to identify the correct parameters that will work
with your protein. As a starting point you can try to set your parameters
based on what as been published in these two papers (there are probably
several other examples in the literature that use different recipes to
calculate the value of the parameters):
Gasper PM, Fuglestad B, Komives EA, Markwick PRL, McCammon JA: Allosteric
networks in thrombin distinguish procoagulant vs. anticoagulant activities.
Proceedings of the National Academy of Sciences 2012, 109:21216-21222
Tikhonova IG, Selvam B, Ivetac A, Wereszczynski J, McCammon JA: Simulations
of
Biased Agonists in the β2 Adrenergic Receptor with Accelerated Molecular
Dynamics. Biochemistry 2013, 52:5593-5603.
Another option is to apply a boost only on the dihedral angles and not on
the rest.
You will have to do some trials and see which set of parameters enable you
to accelerate the sampling of your energy landscape without flattening it
to much.
Good luck,
Eric
On 7 November 2016 at 17:03, Kat G <katwin86.gmail.com> wrote:
> Hi all,
>
> I am using AMD to explore protein conformations (630 residues) in the
> presence and absence of ligand. I used info from CMD at 10ns to calculate
> Ethres and alpha for potential and dihedral from Amber manual. After
> running 30ns of AMD, the backbone RMSD keeps increasing up to 15A. The
> boost energies for potential and dihedral are reported around 1200 and
> 40kcal/mol respectively. Protein structures from AMD trajectories fluctuate
> strongly and seem to be distorted.
>
> Does that mean the boost energy is too high? How can I know my trial
> parameters for AMD work or not (not too high or low boost). And what kind
> of analysis should I try to make sure the enhanced sampling structures are
> acceptable to continue with cluster analysis to finally answer for the
> differences between protein conformations with and without ligand.
>
> Could you please give me any suggestion. Thanks
> Kat
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>
--
Eric Lang
BrisSynBio Postdoctoral Research Associate Modelling
Centre for Computational Chemistry
School of Chemistry - University of Bristol
Bristol BS8 1TS - United Kingdom
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Received on Wed Nov 09 2016 - 02:00:02 PST
