Re: [AMBER] free energy calculation of folding

From: Jason Swails <>
Date: Fri, 29 Jan 2016 10:02:17 -0500

On Fri, Jan 29, 2016 at 3:50 AM, Asmita Gupta <> wrote:

> 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.
> Questions:-
> 1. Can this folding be studied using conventional MD? without introducing
> additional bias?

​I have no idea. I don't think anybody has any idea, really. Look at the
FE barrier from your SMD simulation -- does it seem too high to cross at
standard temperatures?

If you had to use SMD in the first place, I suspect conventional MD won't
work by itself.

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

​You need to define some kind of coordinate for this folding process (maybe
the same one you used for the SMD simulations). Then histogram the MD
trajectory along this reaction coordinate to find the probabilities at each
point. Converting probabilities to free energies is trivial -- FE =
-kT*ln(P_i/P_max)​. But you have to wait for the simulation to get back to
equilibrium (because SMD drives a system *away* from equilibrium).


Jason M. Swails
Rutgers University
Postdoctoral Researcher
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Received on Fri Jan 29 2016 - 07:30:05 PST
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