From: Neema Salimi (nsalimi_at_msg.ucsf.edu)
Date: Fri Sep 07 2007 - 13:02:49 CDT
Arun,
I equilibrated at 500K and ~30 bars, then switched to NVE after the
system stabilized.
Richard,
While your criticism may be valid, it is by no means helpful. Arun
is interested why ubiquitin isn't unfolding in his simulations, not
whether it's the right thing to do. If you don't have some insight
to offer to the list on this topic, perhaps you shouldn't clog up
everyone's inbox.
On Sep 7, 2007, at 5:20 AM, Richard Wood wrote:
> Yes, but I am sure that physiological folding or unfolding of
> proteins didn't occur at 500 K...
>
> 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: "gs_at_mrc-lmb.cam.ac.uk" <gs_at_mrc-lmb.cam.ac.uk>
> To: Arun Krishnan <krishnan_at_ttck.keio.ac.jp>
> Cc: Richard Wood <rwoodphd_at_yahoo.com>; namd-l_at_ks.uiuc.edu
> Sent: Friday, September 7, 2007 1:42:34 AM
> Subject: Re: namd-l: Temperature dependent unfolding..
>
> While Richard's remark applies to the general case, folding proteins
> represent a special case for the way they evolved to get a unique
> native
> conformation. Experimentlists do very nasty things to proteins
> (mutations,
> truncations, addition of huge dyes, dramatic changes of solution
> conditions) and the native conformation of the protein is only
> slightly
> affected. Folding pathways, especially in the region close to the
> native
> state, are a robust feature of the protein, as well. This, along
> with the
> low resolution of available experimental data, are probably the
> reasons
> why many MD unfolding studies (usually involving unphysical
> temperatures
> and pressures) have found a substantial agreement with experimental
> data
> on the transition state for folding. Even if the force field is not
> optimally tuned at those conditions, the unfolding pathways are
> probably
> only partially affected.
> Anyway, great care should always be used when analysing these data, in
> order to distinguish real protein features from force fields
> artifacts.
> In a mechanical unfolding, you are selecting a very special pathway
> out of
> those chaotropically available, that is why the two will not generally
> coincide (unless the specific protein has evolved under the selective
> pressure of mechanical unfolding).
> Gianni
>
> > Thanks to all for your suggestions/comments. I am a little confused
> > though.
> > Since the Phys Rev. paper claimed to see significant unfolding (> 12
> > Angstroms) for simulations at 450 and 520K, they either used a
> higher
> > pressure or something else. Does this mean that unfolding
> simulations, in
> > general, are not to be trusted? I have seen papers where there is
> pretty
> > good fit between experimental and simulated conformations for the
> > transition
> > state etc. Just curious to know what kind of results others have
> obtained
> > here.
> >
> > Also, in a paper which compares thermal unfolding with mechanical
> > unfolding
> > (such as is given in the NAMD tutorial), there seem to be
> significant
> > differences in the unfolding pathway for the two methods..
> >
> > All very confusing!!
> >
> > Cheers,
> >
> > Arun
> >
> > On 9/7/07, Richard Wood <rwoodphd_at_yahoo.com> wrote:
> >>
> >> As I pointed out to Giovanni earlier, as much as we'd like to be
> able
> >> to,
> >> sometimes we can't simulate accurately such processes, as sometimes
> >> there is
> >> a limit as to how we can model the physics of certain situations
> (i.e,
> >> the
> >> diffusion of lipids in a membrane, or the flow of water over a
> crystal
> >> surface of cellulose, two things I've simulated that wound up
> having
> >> "supersonic" velocities), due to the limitations of the code.
> >>
> >> I personally wouldn't put too much stock in someone trying to
> compute
> >> the
> >> unfolding of proteins at this point in time.
> >>
> >> 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<https://mail.google.com/mail?
> view=cm&tf=0&to=rwoodphd_at_yahoo.com>
> >>
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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