Re: Determining Transition State from an Unfolding Simulation

From: Arun Krishnan (krishnan_at_ttck.keio.ac.jp)
Date: Thu Sep 27 2007 - 16:17:15 CDT

Thanks to all.. this does clarify things. (I think the discussion arose from
my query about how to go about determining the transition state from an
unfolding simulation).

Cheers,

Arun

On 9/28/07, Neema Salimi <nsalimi_at_msg.ucsf.edu> wrote:
>
> 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<http://us.rd.yahoo.com/evt=48252/*http://mobile.yahoo.com/mobileweb/onesearch?refer=1ONXIC%3Emobile>
> >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!
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> (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
>
>
>
>
>

-- 
***********************************************
Arun Krishnan, Ph.D,
Assistant Professor,
Institute for Advanced Biosciences,
Keio University,
Center Building,
Tsuruoka, Yamagata 997-0035
Japan
Phone: +81 (0)235-29-0824
Email: krishnan_at_ttck.keio.ac.jp
URL: http://www.iab.keio.ac.jp/~krishnan
**********************************************

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