Re: [AMBER] free energy calculation of folding

From: Asmita Gupta <>
Date: Fri, 29 Jan 2016 14:20:05 +0530

thanks for the response Jason.. i did not explain the problem properly
enough. SMD simulation of my RNA structure, the 5' to 3' (end-to-end)
distance was increased from 50 Ang to 150 Ang. I took snapshots at stages
where this end-to-end distance was 70, 90 and 120 Ang. Now i want to see
the capacity/tendency of these structures to come back to their native
(initial) state from these stages of distortion (by removing the pulling
force). Simply put, i want to see whether they are folding back or not.

1. Can this folding be studied using conventional MD? without introducing
additional bias?

2. How can i study the free energies of this folding process? (if i don't
use umbrella sampling like methods)


On Thu, Jan 28, 2016 at 10:25 PM, Jason Swails <>

> On Thu, Jan 28, 2016 at 7:14 AM, Asmita Gupta <>
> wrote:
> > Dear users,
> >
> >
> > I performed an SMD simulation on a simple RNA duplex structure and
> > calculated the associated PMF values using Jarzynski equality. From SMD
> > trajectory, i have extracted structures at different stages of
> distortion.
> > I removed the external restraints from these structures and performed
> > relaxed conventional MD on them to see how many native contacts can be
> > regained from each stage. Can you please suggest how i can monitor the
> > free energy profiles of these relaxed simulations ?
> >
> ​What do you mean "free energy profiles"? You can't map results from these
> simulations back to what you got doing the Jarzynski averaging (at least
> there's no way I'm aware of to do this, and I doubt it would be
> straightforward if it did exist).
> Also, your steered MD simulations are inherently non-equilibrium, which
> means that you will need to discard part of the relaxation simulations
> until you get back to the true free energy surface (i.e., back to
> equilibrium). Then you can analyze those simulations like any other
> unbiased MD simulation. You could histogram along a degree of freedom to
> construct an unbiased PMF, but you would need sufficient sampling along the
> entire reaction coordinate to converge a meaningful result (which, if you
> could do, would have meant SMD was unnecessary to begin with).
> But maybe I'm not understanding what you are trying to do...
> HTH,
> Jason
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
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Received on Fri Jan 29 2016 - 01:00:03 PST
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