Re: Determining Transition State from an Unfolding Simulation

From: Neema Salimi (nsalimi_at_msg.ucsf.edu)
Date: Thu Sep 27 2007 - 13:22:08 CDT

Hopefully this clears everything up.

Transition State: high energy state (maximum or saddle point on free
energy surface)

Intermediate: metastable state (local minimum on free energy surface)

For protein folding, If one subscribes to transition state theory (or
Kramer's theory), which has some shortcomings for protein folding,
then a two-state folder (i.e. U <---> F) has no intermediates and one
transition state TS. Many proteins have intermediates along the
folding pathway (e.g. barnase), So in that case, you have U <---> I
<---> F and two transition states, TS1 and TS2.

Structures of intermediates can be determined by varying reaction
conditions to favor the intermediate, mutations, etc. (see Im7 from
Sheena Radford's lab). Structures of the transition state cannot be
observed directly and must be inferred from the reaction kinetics,
normally of many mutants and other perturbations (e.g. phi-value
analysis, psi-value analysis).

Computationally, some labs have had success identifying transition
states using unfolding simulations and correlating those structures
to kinetic data (e.g. phi values) of mutants.

And while I think this little discussion may be fruitful, it is not
really germane to NAMD itself, and is much more of a scientific (and
philosophical) question than one of properly running the software.

On Sep 27, 2007, at 9:22 AM, Richard Wood wrote:

> Then I learned different kinetics.
>
> What about A + B ------------->C?
>
> |
> | T1
> | _
> | / \
> FE|\ / \
> | \_/ \
> | \_
> | A+B C
> |
> |
> |
> |-------------------------->
> Reaction pathway
>
> Now, T1 is an intermediate and a transition state.
>
> Richard
>
>
> Richard L. Wood, Ph. D.
> University of Minnesota
> Dept. of Medicinal Chemistry,
> College of Pharmacy
> 717 Delaware St. SE
> Minneapolis, MN 55414-2959
> rwoodphd_at_yahoo.com
>
>
> ----- Original Message ----
> From: Raymond C. Fort Jr. <rcfort_at_maine.edu>
> To: Richard Wood <rwoodphd_at_yahoo.com>
> Sent: Thursday, September 27, 2007 10:39:26 AM
> Subject: Re: namd-l: Determining Transition State from an Unfolding
> Simulation
>
> At 08:34 AM 9/27/2007, you wrote:
> >Isn't an "intermediate" by definition a "transition state"? That's
> >how I learned reaction kinetics.
> >
> >Richard
>
> No. An intermediate is a minimum on the potential energy surface; a
> transition state is a first order saddle point.
>
>
> >Richard L. Wood, Ph. D.
> >University of Minnesota
> >Dept. of Medicinal Chemistry,
> >College of Pharmacy
> >717 Delaware St. SE
> >Minneapolis, MN 55414-2959
> >rwoodphd_at_yahoo.com
> >
> >---- Original Message ----
> >From: paco ty <typaco_at_inbox.com>
> >To: namd-l_at_ks.uiuc.edu
> >Sent: Thursday, September 27, 2007 5:35:14 AM
> >Subject: namd-l: Determining Transition State from an Unfolding
> Simulation
> >
> >I think Richard by "transition state" means more an "intermediate".
> >
> >
> >
> >
> >Yahoo! oneSearch: Finally,
> ><http://us.rd.yahoo.com/evt=48252/*http://mobile.yahoo.com/
> mobileweb/onesearch?refer=1ONXIC>mobile
> >search that gives answers, not web links.
>
> Professor Ray Fort Jr. rcfort_at_maine.edu
> Department of Chemistry chemistry.umeche.maine.edu/fort.html
> University of Maine Voice: (207)-581-1180
> Orono, ME 04469 FAX: (207)-581-1191
>
> Computer modeling of organic and biomolecules; chemistry of lignin
> and cellulose
>
>
>
>
> Boardwalk for $500? In 2007? Ha!
> Play Monopoly Here and Now (it's updated for today's economy) at
> Yahoo! Games.

Neema Salimi
nsalimi_at_msg.ucsf.edu

University of California-San Francisco
Graduate Group in Biophysics
Agard Lab
http://msg.ucsf.edu/agard/
Lab Phone: (415) 476-5143

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