Re: Determining Transition State from an Unfolding Simulation

From: Richard Wood (rwoodphd_at_yahoo.com)
Date: Wed Sep 26 2007 - 11:13:40 CDT

Hi all, What if one were to plot the radius of gyration of the protein as a function of time and plot it? I'm assuming that as it unfolds Rg would increase and hit a maximum and then stay there as it was unfolded? I also assume that you would be looking for Rg max. I've used this in the past to show that a linker peptide wasn't able to pull the binding domain closer to the catalytic domain of an enzyme and then push them apart again; in my case, Rg started out large and then decreased to a constant value and stayed there, no matter how long I ran my simulation. HTH, 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: E. Prabhu Raman <eraman_at_gmu.edu> To: Arun Krishnan <krishnan_at_ttck.keio.ac.jp> Cc: Neelanjana Sengupta <senguptan_at_gmail.com>; namd-l_at_ks.uiuc.edu Sent: Wednesday, September 26, 2007 8:09:07 AM Subject: Re: namd-l: Determining Transition State from an Unfolding Simulation 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 > your treatment... 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 > confidentabout it being right. > > 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 > > > your treatment... > > > > > > 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, > 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 > ********************************************** > ____________________________________________________________________________________ Pinpoint customers who are looking for what you sell. http://searchmarketing.yahoo.com/

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