> On Dec 4, 2014, at 10:28 AM, Kshatresh Dutta Dubey <kshatresh.gmail.com> wrote:
>
> Dear All,
>
> I want to calculate the free energy difference between two conformations
> using Amber. The protein exists in open and closed states and the crystal
> structures are also available. Is there any way where I can simulate
> starting structure (open state) towards a reference structure (closed
> sate). I will be thankful if someone suggests me any idea in this
> direction.
It’s not exactly clear what you want. There’s the idea of a simple potential energy difference between two conformations that you can compute by just doing single-point calculations for both conformations and subtracting them. You could even average over the solvent degrees of freedom using an implicit solvent model to get something closer to a “free energy” difference.
But this is not necessarily interesting -- you don’t have an easy way of declaring those two structures as “representative” of the two states you are trying to compare. Because in reality, you are _not_ comparing two states -- you are comparing two different (and still very large) portions of phase space that are made up of a Boltzmann-weighted average of many states.
Ergo, “free energy” differences between those two states are, in my opinion, a lot more interesting and meaningful. To do this, you need to sample both states using something like MD or Monte Carlo. If your simulation samples both states and transitions between them several times in your simulation, you can simply compute their free energies directly. If not, you may need to use some kind of enhanced sampling technique to jump over those barriers, like umbrella sampling or accelerated MD, for instance, and reweight to get the unbiased free energy difference.
HTH,
Jason
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Thu Dec 04 2014 - 12:30:04 PST
