>>2. How can i study the free energies of this folding process? (if i don't
use umbrella sampling like methods)
Having done your steered MD you can relate the equilibrium free energy
differences to the non-equilibrium work done at different stages of the
path, using Crook's theorem.
Basic explanation and tutorial here:
http://www3.mpibpc.mpg.de/groups/de_groot/compbio2/p10/index.html#intro
Fuller exposition here:
https://www.mpibpc.mpg.de/275668/Goette_2009_JCC_30_447-457.pdf
Non equilibrium work done is the integral dE/dlambda where E is (potential
+ kinetic) energy of the system and lambda is the coordinate that you are
steering along.
>>>>*Jason:* I suspect that what you want to do is somewhere between
extremely difficult to currently impractical
... free energy from steered MD is easy in theory ...... :-D actually no I
wouldn't advise a beginner to approach this calculation without informed
supervision either.
Josh
On 29 January 2016 at 16:15, Carlos Simmerling <carlos.simmerling.gmail.com>
wrote:
> you might want to look at some of the literature on RNA simulations. Lab
> like those of Tom Cheatham, Angel Garcia, and others, have looked at how
> challenging it is to get free energy data for RNA systems, as well as the
> reliability of RNA force fields. I suspect that what you want to do is
> somewhere between extremely difficult to currently impractical, but without
> knowing more about your specific system we can't really help. Look at Tom's
> papers (especially recent ones from Christina Bergonzo) to get an idea how
> this might be done.
>
> On Fri, Jan 29, 2016 at 10:02 AM, Jason Swails <jason.swails.gmail.com>
> wrote:
>
> > On Fri, Jan 29, 2016 at 3:50 AM, Asmita Gupta <asmita4des.gmail.com>
> > wrote:
> >
> > > thanks for the response Jason.. i did not explain the problem
> properly
> > > enough.
> > >
> > > ..in 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).
> >
> > HTH,
> > Jason
> >
> > --
> > Jason M. Swails
> > BioMaPS,
> > Rutgers University
> > Postdoctoral Researcher
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> >
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Received on Wed Feb 03 2016 - 04:30:03 PST
