From: Christopher Harrison (char_at_ks.uiuc.edu)
Date: Thu Sep 27 2007 - 15:43:54 CDT
In mechanistic descriptions of reacting atoms, an intermediate, per
McMurray (1st edition, I believe) page 114, "is not itself a
transition state, but neither is it a stable, isolable product." It
cannot be placed in a bottle. Classical examples are cations,
anions, or radicals. However, it is not uncommon to hear the term
"intermediate" used in informal discussions to describe the isolable
product connecting two consecutive reactions.
In any case, this semantics issue might be resolved for future
listserv readers by two key questions that carefully define the terms
we are using:
1. Is an intermediate the same thing as a transition state? In
classical Eyring and RRKM transition state theory (TST) the
"intermediate" and the "transition state" are not the same thing.
For those interested in more detailed descriptions of each state,
please refer to earlier posts in this thread by several members
(Peter Freddolino, Lewyn, Raymond Fort, Chris Harrison, and Thomas
Gaillard. My apologies to anyone I missed. :-) ). The following
references may also be of use:
Atkins, P.W., Physical Chemistry, 5th ed (1994) page 403
Atkins, P.W., Physical Chemistry, 6th ed (1998) page 701
Laidler, K.J., Chemical Kinetics, 3rd ed (1987) page 208
2. Is classical TST an appropriate model to describe the kinetics of
conformational change in biomolecules? As I understand it, TST
requires a little "patching" to work for protein folding. The
"transition state" is replaced with a "transition state
ensemble" (TSE) which is not a collection of "transition state"
structures.
Transition state ensembles, as defined by Onuchic, are ensembles of
structures through which the system must pass to fold. "They do not
consist of saddle points on the energy surface but are rather high
energy intermediate structures" in this bottlenecked region of the
potential energy surface that are suggested to explain experimentally
observed exponential folding kinetics. For those interested, and the
most relevant responses to Arun's original question, please see
earlier posts by Prabhu Raman, Neelanjana Sengupta and Lewyn. The
following may also be potential starting places:
Onuchic et al, Curr Opin Struct Biol, 14:70-75 (2004)
Onuchic et al, PNAS 92:3626-3630 (1995)
In summary, a "transition state" is not the same thing as a
"transition state ensemble." And an intermediate (within the context
of TST), per McMurray (1st edition, I believe) page 114, "is not
itself a transition state, but neither is it a stable, isolable
product." I do not know how the protein-folding community defines
"intermediate" or if it is considered isolable. Perhaps someone in
the protein-folding community could suggest an answer?
At any rate, I must agree with Neema that this is more of a
philosophical / scientific question than a technical question of
running the NAMD software.
Cheers,
Chris
Christopher Harrison Ph.D.
Postdoctoral Research Associate
Theoretical and Computational Biophysics Group
Beckman Institute
University of Illinois at Urbana-Champaign
405 N. Mathews
Urbana, IL 61801
char_at_ks.uiuc.edu
On Sep 27, 2007, at 12:08 PM, Richard Wood wrote:
> Then they're talking about something ENTIRELY different than what I
> am. An intermediate IS not a TS. You can't mix apples and
> oranges, and that is what is being done. An intermediate can be
> isolated, a TS cannot.
>
> The original poster is looking for an intermediate structure in the
> process of folding or unfolding, which is a conformation that could
> exist on its own, and not a TS.
>
> 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: Christopher Harrison <char_at_ks.uiuc.edu>
> To: Richard Wood <rwoodphd_at_yahoo.com>
> Cc: namd-l_at_ks.uiuc.edu
> Sent: Thursday, September 27, 2007 11:45:16 AM
> Subject: Re: namd-l: Determining Transition State from an Unfolding
> Simulation
>
> Raymond is correct. The classical definition of an intermediate is
> a short-lived, experimentally observable species that is at a local
> minimum on the potential energy surface (PES) between transition
> states. A transition state structure must be a first order saddle
> point on the PES where the single negative frequency corresponds to
> the mode of motion describing the collective coordinate change. A
> transient structure that possesses any negative frequencies is not
> defined as an "intermediate."
>
> Chris
>
>
>
> Christopher Harrison Ph.D.
> Postdoctoral Research Associate
> Theoretical and Computational Biophysics Group
> Beckman Institute
> University of Illinois at Urbana-Champaign
> 405 N. Mathews
> Urbana, IL 61801
> char_at_ks.uiuc.edu
>
>
>
>
> On Sep 27, 2007, at 11:22 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.
>
>
>
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