Re: [AMBER] free energy profile

From: <>
Date: Wed, 9 Jun 2010 03:16:26 -0400 (EDT)

Hi Lars,

> Given two long MD simulations (NVE) of the same protein that sample
> two different conformational spaces (e.g. an opening vs a more fixed
> conformation due to nucleotide binding), would it be possible to
> calculate a free energy profile that can be related to the
> conformations in the trajectory?

If the two subspaces of the conformational space simulated in the two MDs
overlap, then yes, you should be able to do something like a two-window
umbrella sampling by hand. All you need to do is define a reaction
coordinate and make histograms of your structures along that. Technically
you would just be doing US with a zero additional potential.

> Is this only possible by performing an umbrella sampling, or would it
> make sense to extract internal energies and solvation terms and relate
> this to the conformational changes somehow?

The energies already did their work in my opinion, the probability to
observe a given conformation should already be related to its free energy.

> In regard to umbrella sampling, would it be reasonable to perform it
> to drive large scale conformational changes? i.e. by driving an
> opening of the protein (300? residues) based on angle/distance
> restraints on the structure (where the restraints are set between
> center of masses of two/three domains in the protein). Or should it be
> limited to smaller conformational changes, as atom-atom restrains?

I believe, as long as you can get converged simulations (a big 'if'!) any
change can be analyzed that way. The difficulty may be in finding a good
reaction coordinate to drive your system along. Maybe for a case like
this, a NEB simulation would be preferable?

Kind Regards,


Dr. Thomas Steinbrecher
BioMaps Institute
Rutgers University
610 Taylor Rd.
Piscataway, NJ 08854

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Received on Wed Jun 09 2010 - 00:30:04 PDT
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