# Re: Determining Transition State from an Unfolding Simulation

From: E. Prabhu Raman (eraman_at_gmu.edu)
Date: Wed Sep 26 2007 - 08:09:07 CDT

Neelanjana:
>see if it is stable over an extended period of time.
> If you
> find that the energy is stable too, then you "may" think that you have
> encountered a transition state. However, a lot of caution is
> required in

I do not understand your point of finding a stable state. During a constant temperature run, the transition state will be populated for a "short" time right? (as by definition the transition state is the maximum of Free energy as a function of the reaction coordinate) Then why are we detecting a stable state? (I think by this, we will end up detecting the equilibrium state at the simulation temperature and not the transition state)

Arun: You have complete unfolding trajectory right? i.e you start from a fairly folded state and end at a unfolded state where most native contacts are lost ? Because if the trajectory is not complete, then detecting the transition state(s) using snapshots showing steep buildup of reaction coordinate might not be right.

-Prabhu

E.Prabhu Raman
Ph.D Student, Bioinformatics & Computational Biology
George Mason University

----- Original Message -----
From: Arun Krishnan <krishnan_at_ttck.keio.ac.jp>
Date: Wednesday, September 26, 2007 0:56 am
Subject: Re: namd-l: Determining Transition State from an Unfolding Simulation

> Hi Prabhu and Neelanjana,
>
> Thanks for your inputs... Shall try them out and let you know what
> I get. To
> answer Neelanjana's point, yes, my unfolding simulation does seem
> to follow
> the same pathway as has been shown in literature... so am fairly
>
> Cheers,
>
> Arun
>
> On 9/24/07, E. Prabhu Raman <eraman_at_gmu.edu> wrote:
> >
> > Using Snapshots of a trajectory of Kinetics simulation at a constant
> > temperature, a method called Progress Variable Cluster has been
> used to
> > pin-point the structures of the transition state ensemble(TSE).
> > REF : Chemical Physics Volume 307, Issues 2-3, 27 December 2004,
> Pages> 251-258
> > The basic idea being that the passage through the transition
> state can be
> > identified by the time-point(s) that record a maximal change in
> a suitable
> > reaction coordinate (example Rg, or number of native contacts)
> > However,I WOULD CAUTION that this approach,to my best knowledge
> has been
> > tried for Coarse Grained Model folding studies and more importantly
> > lots(~100) of independent trajectories were used to get a
> picture of the
> > TSE.
> > I assume that you might not have too many unfolding
> trajectories. But
> > since this procedure is easy to apply, you can try it out and
> compare your
> > TSE from any experimental available data(phi-values).
> > The reference given above uses a clustering algorithm to cluster
> similar> structures. A first pass at TSE determination could be
> not to cluster, but
> > simply pick out the structures that record the steepest
> buildup(or down) of
> > the reaction coordinate and look at the structures to see if it
> is any
> > meaningful at all.
> >
> > Best
> > Prabhu
> >
> > E.Prabhu Raman
> > Ph.D Student, Bioinformatics & Computational Biology
> > George Mason University
> >
> > ----- Original Message -----
> > From: Neelanjana Sengupta <senguptan_at_gmail.com>
> > Date: Sunday, September 23, 2007 7:33 pm
> > Subject: Re: namd-l: Determining Transition State from an Unfolding
> > Simulation
> >
> > > Hi,
> > >
> > > This would work (if at all) assuming your unfolding pathway
> > > retraces the
> > > protein folding pathway. If you figure out a way to determine if
> > > this is
> > > what is going on (figuring this out would indeed be non-trivial),
> > > you may
> > > then closely examine the timeline of a unfolding parameter
> (Rg, for
> > > instance) and see if it is stable over an extended period of time.
> > > If you
> > > find that the energy is stable too, then you "may" think that
> you have
> > > encountered a transition state. However, a lot of caution is
> > > required in
> > >
> > > Would be great if others share their thought too!
> > >
> > > Cheers,
> > > Neelanjana
> > >
> > > On 9/23/07, Arun Krishnan <krishnan_at_ttck.keio.ac.jp> wrote:
> > > >
> > > > Hi All,
> > > >
> > > > Is there a way to calculate the transition state structure from
> > > Unfolding> data? From the plot of RMSD vs time maybe?
> > > > Or is there some other way? Any pointers would be much
> appreciated.> > >
> > > > Cheers,
> > > >
> > > > Arun
> > > >
> > > >
> > > >
> > >
> > >
> > > --
> > >
> >
>
>
>
> --
> ***********************************************
> Arun Krishnan, Ph.D,
> Assistant Professor,