Hi Jason,
Thanks for your reply. The single point energy of two states and then their
difference as free energy, I think, doesn't seem very interesting without
proper sampling. I am looking something like umbrella sampling or Steered
MD. But in amber advanced tutorial/manual, I didn't get information to put
one state/coordinate as a reference and to drive initial structure towards
reference so that we can get the potential of mean force for this
conformational transition as we can get in umbrella sampling. So, is there
any way in this direction? I found in NAMD, one can define collective
variables but I am easy with amber and wiling to do similar calculation
using Amber.
Regards
Kshatresh
On Thu, Dec 4, 2014 at 10:20 PM, Jason Swails <jason.swails.gmail.com>
wrote:
>
> > 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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> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
With best regards
************************************************************************************************
Kshatresh Dutta Dubey
Post Doctoral Researcher,
Lise Meitner Center for Computational Quantum Chemistry
Hebrew University of Jerusalem Israel
Jerusalem, Israel
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Received on Thu Dec 04 2014 - 13:30:04 PST
